Hung-Chieh Chou

Handwashing Program for the Prevention of Nosocomial Infections in a Neonatal Intensive Care Unit

OBJECTIVE To evaluate the effects of a hand hygiene program on compliance with hand hygiene and the rate of nosocomial infections in a neonatal intensive care unit (NICU). DESIGN Open trial. SETTING A level-III NICU in a teaching hospital. PARTICIPANTS Nurses, physicians, and other healthcare workers in the NICU. INTERVENTIONS A multimodal campaign for hand hygiene promotion was conducted beginning in September 1998. This program consisted of formal lectures, written instructions and posted reminders regarding hand hygiene and proper handwashing techniques, covert observation, financial incentives, and regular group feedback on compliance. Surveillance of handwashing compliance and nosocomial infections before and during the program was analyzed. RESULTS Overall compliance with hand hygiene improved from 43% at baseline to 80% during the promotion program. The rate of nosocomial infections decreased from 15.13 to 10.69 per 1,000 patient-days (P = .003) with improved handwashing compliance. In particular, respiratory tract infections decreased from 3.35 to 1.06 per 1,000 patient-days during the handwashing campaign (P = .002). Furthermore, the correlation between nosocomial infection of the respiratory tract and handwashing compliance also reached statistical significance (r = -0.385; P = .014). CONCLUSIONS Improved compliance with handwashing was associated with a significant decrease in overall rates of nosocomial infection and respiratory infections in particular. Washing hands is a simple, economical, and effective method for preventing nosocomial infections in the NICU.

Parental Smoking During Pregnancy and Its Association with Low Birth Weight, Small for Gestational Age, and Preterm Birth Offspring: A Birth Cohort Study

BACKGROUND Intrauterine exposure to tobacco smoke has been discerned as an important risk factor for low birth weight (LBW), small for gestational age (SGA), and preterm birth infants. In this cohort study, we investigated the association of the amount of parental smoking during the different pregnancy stages with birth weight and the incidence of preterm delivery. METHODS Our study population was acquired from the Taiwan Birth Cohort Study. Between June 2005 and July 2006, 21,248 postpartum women were interviewed 6 months after their deliveries by a structured questionnaire. The parents were divided into four groups according to the amount of smoking during preconception, the first trimester, and the second and third trimesters. The relationships of parental smoking with gestational age and birth weight during the different pregnancy stages were assessed using multivariate linear regression. Multiple logistic regression analyses were performed to estimate the odds ratios and 95% confidence intervals of preterm delivery, LBW, and SGA infants during the different parental smoking status and the different pregnancy stages. RESULTS After adjusting for the physical and socioeconomic status of the parents and for paternal smoking during the same period, we found that maternal smoking decreased birth weight. Compared with the nonsmoking groups, all the maternal smoking groups had higher incidences of LBW, SGA, and preterm birth infants, especially when the mothers smoked >20 cigarettes/day. The association of paternal smoking with LBW, SGA, and preterm birth infants was insignificant. CONCLUSION Maternal smoking is responsible for increased incidences of LBW and preterm delivery of babies, and therefore, smoking cessation/reduction should be advised to pregnant women to reduce morbidities in their neonates. Further studies are needed to clarify the correlation of fetal health with passive smoking, including exposure to environmental tobacco smoke and to other smokers in the family.

Excess Soluble fms-Like Tyrosine Kinase 1 and Low Platelet Counts in Premature Neonates of Preeclamptic Mothers

Objective. To investigate the relationship of neonatal platelet count and preeclampsia to levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the cord blood of preterm infants. Methods. Sixty-nine preterm infants with a gestational age between 26 and 37 weeks at birth were enrolled. sFlt-1, PlGF, and VEGF levels in the cord blood of preterm neonates, with or without maternal preeclampsia, were measured using a standardized sandwich enzyme-linked immunosorbent assay method. Results. Infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF levels. There was a significantly positive relationship between neonatal platelet count and birth weight and a significantly negative relationship between neonatal platelet count and cord blood sFlt-1 levels. Multiple regression analysis revealed that only birth weight and cord blood sFlt-1 levels were independently related to neonatal platelet count, whereas maternal preeclampsia, gestational age (GA), and small for GA (SGA) were not related. Neonates with thrombocytopenia had higher cord blood sFlt-1 levels but lower birth weight. A significant correlation was also found between birth weight and cord blood sFlt-1 levels. Multiple regression with birth weight as the dependent variable found that only GA and cord blood sFlt-1 levels were independently related. Furthermore, infants with high cord blood sFlt-1 were more likely to have lower platelet count and maternal preeclampsia, be SGA, and have a trend toward lower birth weight. Conclusion. Excess sFlt-1 may play an important role in the development of maternal preeclampsia- induced neonatal thrombocytopenia, and SGA.

Neonatal Sepsis: A 6-Year Analysis in a Neonatal Care Unit in Taiwan

BACKGROUND Neonatal sepsis is the most serious problem in neonatal intensive care, resulting in significant morbidity and mortality. We evaluated the causative pathogen, drug sensitivity, hematological parameters, clinical course and mortality rate of neonatal sepsis in a Taiwanese medical center and compared our results to those of previous studies conducted in Taiwan. METHODS Neonates admitted to the neonatal intensive care unit (NICU) at National Taiwan University Hospital (NTUH) between January 2001 and December 2006 were included in this study. Patients were divided into early-onset sepsis and late-onset sepsis groups if their culture tested positive within the first 7 days of life or later, respectively. RESULTS A total of 109 episodes of sepsis were identified in 100 neonates. The incidence of sepsis was 4.06% among all NICU admissions. Most neonates with early-onset sepsis were term infants, while very low birth weight (VLBW) and preterm infants accounted for the majority of cases of late-onset sepsis. In early-onset sepsis, the most common pathogens responsible included group B streptococci (GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was associated with more meningitis involvement but lower incidence of mortality compared with E. coli. The most common causative microorganisms in late-onset sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The sepsis-related mortality rates were higher in early-onset sepsis (10%) than in late-onset sepsis (7%). CONCLUSION Unlike previous reports from Taiwan, in the present study, GBS was found to be the leading pathogen in early-onset sepsis. GBS screening and intrapartum antibiotic prophylaxis guidelines should be used in Taiwan to prevent early neonatal sepsis. The most common causative microorganisms of late-onset sepsis were CONS and Candida species. Candida parapsilosis was associated with a high mortality rate.

Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis

Objective:To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis. Design:Randomized prospective experimental study. Setting:University medical laboratory. Subjects:Male C56BL/6 strain mice. Interventions:We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated. Measurements and Main Results:Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflammatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis. Conclusions:These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.

Lipopolysaccharide-induced Notch signaling activation through JNK-dependent pathway regulates inflammatory response.

BackgroundNotch and TLR pathways were found to act cooperatively to activate Notch target genes and to increase the production of TLR-induced cytokines in macrophages. However, the mechanism of LPS-induced Notch activation and its role in sepsis still remains unclear.MethodsWe analyzed the expression patterns of Notch components in a LPS-stimulated murine macrophage cell line using real-time PCR and western blotting. The role of DAPT, a gamma-secretase inhibitor that is known to be a potent Notch inhibitor, in LPS-induced cytokine release and experimental sepsis in mice was also explored. Students t-test was used to analyze the difference between the two groups.ResultsWe found that Notch signaling was activated after LPS stimulation. The expression of Jagged 1, a Notch ligand, induced by LPS occurred in a JNK-dependent manner. In addition, Notch target genes were upregulated by early Notch-independent activation followed by delayed Notch-dependent activation after LPS stimulation. Disruption of Notch signaling by DAPT attenuated the LPS-induced inflammatory responses, including vascular endothelial growth factor (VEGF) and high-mobility group box chromosomal protein 1 (HMGB1), both in vitro and in vivo and partially improved experimental sepsis survival.ConclusionsThese findings support the existence of a synergistic effect of Notch signaling and the LPS pathway both in vitro and in vivo. Therefore, in the future Notch inhibitors may be utilized as adjunctive agents for the treatment of sepsis syndrome.

Rehospitalization of extremely-low-birth-weight infants in first 2 years of life

AIMS To determine whether (1) chronic lung disease (CLD) is the prime reason for extremely-low-birth-weight (ELBW) infant readmission during the first 2 years of life, (2) surfactant and other advanced therapies have reduced ELBW infant readmissions, (3) home oxygen therapy (HOT) is efficacious for this group. STUDY DESIGN The hospital records of these ELBW infants were reviewed retrospectively. Data on age, diagnosis, treatment, and duration of each hospitalization were compiled and analyzed for their association to CLD and to readmission for CLD and other reasons. SUBJECTS All 60 surviving infants with a birth body weight of less than 1001 g (ELBW) born from January 1993 to February 1998 were followed up to 2 years (mean 20.4 +/- 7.4 months) to evaluate their respiratory outcome. RESULTS Forty-two percent of these infants developed CLD. Upon discharge from the hospital, 28% (7/25) of the patients were given HOT for a median period of 60 days. Of the 47 ELBW infants who were studied the entire 2-year period, 72% were readmitted. Infants with CLD were readmitted more frequently (p=0.045) and had longer hospital stays during the first 2 years of life (p=0.034) than those without CLD. Respiratory illness was the main reason for readmission (55%) of these ELBW infants. The incidence of readmission due to respiratory tract infection was not significantly different in infants with CLD (61%) and infants without respiratory complications (44%) (p=0.159). CONCLUSIONS Infants with CLD (whether receiving HOT or not) showed no higher readmission rate due to respiratory infection, but the HOT group did have higher morbidity. The premature lung itself rather than the presence of CLD, as we would expect, makes ELBW infants more prone to readmission for respiratory illness.

Serial measurements of serum alkaline phosphatase for early prediction of osteopaenia in preterm infants.

Aim:  Osteopaenia commonly occurs in preterm infants; however, its diagnosis is often delayed when based on radiological findings. The aim of this study was to examine whether serial measurements of bone turnover markers are useful for early prediction of osteopaenia in preterm infants.

Antenatal treatment of chylothorax and cystic hygroma with OK-432 in nonimmune hydrops fetalis.

Objectives: To present our experience of using OK-432 in treating fetal cystic hygroma and chylothorax complicated with nonimmune hydrops fetalis. Methods: OK-432 (Picibanil®) was injected into the fetal pleural cavity or fetal cystic hygroma. Results:Patient 1: A 23-year-old, gravida 2, para 1, was found to have a recurrent fetal chylothorax at GA 29 weeks. Serial amnioreduction and thoracocentesis was performed at GA 31, 32, 33, and 34 weeks. Intrapleural OK-432 injection was performed twice at GA 33 and 34 weeks. Cyanosis and respiratory distress were noted immediately after birth (GA 34 weeks). The baby expired despite of aggressive neonatal resuscitation. Patient 2: A 26-year-old, gravida 2, para 1, was found to have a cystic hygroma of her fetus at GA 17 weeks. Karyotype of the cystic fluid and the amniocytes were 46, XY. Fetal ascites developed at GA 22 weeks. OK-432 injection into the tumour was performed at GA 23 weeks. Stabilization of the cystic hygroma was noted throughout the pregnancy (about 3.5 cm in diameter). Serial fetal paracentesis and/or amnioreduction were performed. Karyotype of the ascites was again 46, XY. Maternal dietary modification with medium chain triglyceride was also prescribed. Chylothorax developed and the baby was born by cesareans at GA 32 weeks. Resolution of pleural effusion, ascites, and regression of cystic hygroma were noted since the 2nd day after birth. The baby had survived beyond 4 months of age at submission. Conclusion: Combination of antenatal OK-432 injection, maternal dietary modification, serial thoracocentesis plus paracentesis, together with amnioreduction and tocolysis, appeared to contribute to the success of antenatal treatment. Fetal pulmonary expansion may determine the immediate neonatal survival.

Management of Congenital Cystic Adenomatoid Malformation and Bronchopulmonary Sequestration in Newborns

BACKGROUND Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental anomalies. Early surgical excision is becoming an increasingly common option. We investigated the clinical features and management of patients with CCAM and BPS at the National Taiwan University Hospital. METHODS We conducted a retrospective review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995 to January 2008. Prenatal examination, postnatal presentation, management and patient outcome were analyzed. We also propose a concise algorithm for the practical management of these conditions. RESULTS Sixteen patients were recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%) with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed antenatally at a median gestational age of 20 weeks. Eleven (69%) patients underwent surgical resection before 6 months of age because of respiratory distress or repeated pulmonary infection. There were no surgery-related complications among the seven patients who underwent early surgery within 1 month of age. Five (31%) patients remained asymptomatic and did not undergo surgery. All patients survived with no limitations to daily activity during follow-up periods of 1-8 years. CONCLUSION The high proportion of mixed-type lesions suggests that CCAM and BPS may share the same developmental ancestry. Early surgical resection within 1 month of age is safe in symptomatic patients.