System-based strategy for the management of meconium aspiration syndrome: 198 consecutive cases observations.

To evaluate whether the system-based strategy for management of meconium aspiration syndrome (MAS) could reduce the morbidity and mortality rate of MAS in our institute, a prospective consecutive clinical observation was conducted. System-based strategy including appropriately trained the relevant medical staff to familiar with neonatal resuscitation program, early surfactant replacement or lavage following with high-frequency ventilator (HFV) and/or inhaled nitric oxide (iNO). Outcome measurements were the morbidity and mortality rates of MAS. All infants of MAS in the study period were included except cases of congenital malformations or cyanotic congenital heart disease (CHD). Oxygen, nasal continuous positive airway pressure (CPAP), and intermittent mandatory ventilation (IMV) were applied as clinically indicated. Surfactant was used as replacement or lavage therapy for MAS infants whose oxygen index (OI) exceeded 20 or value for AaDO2 exceeded 400 within 6 hours of age. High-frequency oscillator ventilation (HFO) was applied for infants of MAS that demonstrated intractable respiratory failure with conventional mechanical ventilation and 100% oxygen. Inhaled nitric oxide (iNO) was used with IMV or HFO for infants of persistent pulmonary hypertension (PPHN) when it was unresponsive to conventional therapy. Dexamethasone was prescribed in infants of severe hypotension that did not respond to dopamine and epinephrine. A series of 198 consecutive infants of MAS born in this hospital during 9 years were analyzed. There was no mortality. Fourteen infants developed PPHN, 11 had pneumothorax, 1 had pulmonary hemorrhage, 2 had neurologic sequelae because of severe asphyxia, and 2 developed bronchopulmonary dysplasia. Our results indicated that appropriately trained relevant medical staff with neonatal resuscitation program to avoid complicated MAS and early surfactant replacement or lavage following with HFO and/or iNO could reduce the morbidity and mortality rate of MAS even without extracorporeal membrane oxygenation (ECMO).

Epidemiologic trends in nosocomial bacteremia in a neonatal intensive care unit.

The primary goal of this study was to analyze the epidemiologic features of nosocomial bloodstream infection (NBSI) in a neonatal intensive care unit over a 7-year period. All neonatal patients with NBSI treated from January 1997 to December 2003 were retrospectively analyzed. 232 NBSI episodes were diagnosed in 208 patients. The average NBSI patient-day rates were 4.69 and 2.59 per 1000 patient-days in 1997-1999 and 2000-2003, respectively. The average NBSI rates were 5.00 and 1.50 per 1000 patient days in neonates <1500 g and > or =1500 g, respectively. The proportion of Gram-positive organisms increased from 24% in 1997-2001 to 41% in 2002-2003, whereas the proportion of Gram-negative isolates decreased from 65% in 1997-2001 to 47% in 2002-2003. The implementation of measures for the prevention of nosocomial infection was associated with the reduction of NBSI rates. Low birth weight was demonstrated to be a significant risk factor for NBSI. The fact that Gram-positive organisms were isolated in increasing frequency may impact on the appropriate selection of empiric antimicrobial therapy for NBSI in the neonatal intensive care unit.

Interleukin-8 in bronchoalveolar lavage fluid of premature infants at risk of chronic lung disease.

BACKGROUND AND PURPOSE: Persistence of neutrophils in the tracheal fluid of premature infants is associated with chronic lung disease (CLD). Interleukin-8 (IL-8) is a potent neutrophil chemoattractant. This study investigated whether IL-8 is increased in the bronchoalveolar lavage fluid of premature infants with different types of CLD. METHODS: Forty two very low birth weight infants who required mechanical ventilation were recruited. Twenty eight of these infants developed CLD and 14 infants recovered without developing CLD. Four additional infants receiving mechanical ventilation for non-respiratory reasons were also enrolled as controls. CLD was defined as requirement for supplemental oxygen at 28 days of age and chest radiograph showing characteristic appearance. CLD was further classified into 3 subtypes: bronchopulmonary dysplasia (BPD), Wilson-Mikity syndrome (WMS) and chronic pulmonary insufficiency of prematurity (CPIP). RESULTS: IL-8 in bronchoalveolar lavage fluid was significantly increased in the CLD group by 8 days of age compared to those who did not develop CLD (p < 0.05). For infants without CLD, IL-8 increased from 963 pg/mL on day 1 after delivery to 1463 pg/mL on day 4, and decreased to 1,000 pg/mL on day 8. For infants with BPD, IL-8 increased from 925 pg/mL on day 1 after delivery to 2,650 pg/mL on day 8, and then gradually decreased to 1,500 pg/mL on day 28. Infants with WMS had significantly higher IL-8 from the first day after delivery (4,567 pg/mL) than infants with BPD or CPIP and this difference persisted to age 28 days (2475 pg/mL). CONCLUSIONS: Persistent inflammation could be a major contributory factor in the development of CLD. The different patterns of response to inflammation in different types of CLD may have implications for the design of appropriate strategies to prevent and treat CLD.

Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. PATIENTS AND METHODS: A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2). RESULTS: Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species. CONCLUSION: Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.

Role of antibiotics in management of non-ventilated cases of meconium aspiration syndrome without risk factors for infection.

There are limited data on the efficacy of antibiotics in the management for meconium aspiration syndrome (MAS). This purpose of the prospective randomized controlled clinical trial compared the infection-related outcome of non-ventilated cases of MAS without perinatal risk factors for infection, treated with or without antibiotics therapy, as measured by the incidence of pneumonia and sepsis up to the age of 2 months. From January 1997 to July 2003, this study was carried out in our nursery. Infants with MAS without perinatal risk factors for infection and without ventilator use were randomly allocated to study and antibiotics groups after informed parental consent was obtained. The study group did not receive antibiotics, while the antibiotics group received antibiotics including ampicillin and gentamicin for 3 days until the blood cultures were negative, as was standard practice in the nursery. Other management and monitoring of MAS were the same in both groups. Of a total of 425 cases of MAS, 119 cases were excluded because there were at risk for infection or respiratory failure needing ventilator support. The study group comprised 148 cases and the antibiotics group 158 cases. Among these patients, 127 from the study group and 132 from the antibiotics group were followed up until 2 months of age. The profile of patients with respect to the method of delivery, the characteristics of meconium, Apgar score, sex, gestational age and birth body weight was similar in both groups. There were no significant differences in the duration of tachypnea, O2 supplementation and nasal continuous positive airway pressure (CPAP) between the two groups. Pneumothorax occurred in 4 cases in the study and 7 cases in the control group. There was no mortality in either group. Blood cultures at 6 and 72 h of age were all negative in both the study and the antibiotics groups. No infant developed bacterial pneumonia, sepsis or meningitis in the follow-up program at 2 months of age. We conclude that antibiotic treatment did not affect the clinical course and outcome related to infection in MAS without perinatal risk factors for infection and without ventilator use. The role of antibiotics in the management of MAS may need to be reevaluated in a study with a larger sample size.

Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn.

Clinical experience indicates that persistent pulmonary hypertension of the newborn (PPHN) is one of the major causes of death in infants with meconium aspiration syndrome (MAS). We aimed to investigate the risk factors associated with MAS which lead to PPHN in order to search for ways to reduce the mortality associated with MAS. From 1995 to 2003, we conducted a retrospective study of infants with MAS at the China Medical University Hospital. We compared the risk factors associated with MAS, including pattern of fetal heart beat, mode of delivery, apgar score, sex, gestational age, birth body weight, in born or out born infants, resuscitation before admission, first pH at admission, asphyxia, surfactant usage, pneumothorax, pulmonary hemorrhage and shock before the diagnosis of PPHN between PPHN and non PPHN infants. During the nine-year study, 362 infants with MAS were enrolled. There were 64 infants with (17.7%) PPHN and 298 infants without PPHN. According to univariant analysis, the significant risk factors associated with MAS which lead to PPHN were out born infant (p=0.007), change of fetal heart beat pattern (p=0.0001), resuscitation before admission (p=0.0001), low pH (p=0.002), asphyxia (p<0.0001), shock (p<0.0001), pneumothorax (p=0.0004), and pulmonary hemorrhage (p<0.0002). Based on the results of logistic regression analysis, the risk factors were pneumothorax (p=0.04, odds ratio: 2.34), change of fetal heart beat pattern (p=0.02, odds ratio: 2.37) and asphyxia (p=0.001, odds ratio: 5.48). We conclude that pneumothorax, change of fetal heart beat pattern and asphyxia are the most important risk factors associated with MAS which lead to the development of PPHN. Avoidance of asphyxia and pneumothorax might be the key to reduce the incidence of PPNH and mortality rate of MAS.

Evaluation of the severity of chronic lung disease in premature infants by pulse oximeter.

Three parameters obtained by pulse oximeter were tested to assess the severity of chronic lung disease (CLD) in premature infants. The FiO2 required to keep oxygen saturation of 90% on pulse oximeter at rest condition was defined as FiO2Sp90. The value of oxygen saturation with a FiO2 of 0.21 at rest was defined as room air saturation. The percentage of the time duration that oxygen saturation exceeded 90% during the measurement with the FiO2Sp90 was defined as time-percentage of SpO2 > or = 90% with FiO2Sp90. These parameters were monitored for 60 minutes once weekly in very low birth weight infants for at least 4 weeks beginning at 34 weeks of postconceptional age. Thirty-four infants were enrolled; 13 of them had CLD. There were totally 57 measurements in 13 infants with CLD, and 84 measurements in 21 infants with no CLD. Values of each parameter significantly correlated with the FiO2 used during the measurement; the FiO2Sp90 had positive correlation with FiO2 (r = 0.991, p < 0.001), the room air saturation and time percentage of SpO2 > 90% with FiO2Sp90 had negative correlation (r = -0.975, p < 0.001 and r = -0.668, p < 0.05, respectively). In the serial measurements, room air saturation improved even after the FiO2Sp90 reached 0.21. Time-percentage of SpO2 > or = 90% with FiO2Sp90 showed increase with age even after the room air saturation reached over 90%. Therefore, room air saturation was more sensitive than FiO2Sp90, and the time-percentage of SpO2 > or = 90% with FiO2Sp90 was more sensitive than room air saturation in estimating the severity of CLD. For clinical use, FiO2Sp90 may be used as a guide for oxygen concentration required. Room air saturation may offer a criterion in deciding the need of further oxygen therapy, and time-percentage of Sp02 > or = 90% with FiO2Sp90 could be used to follow up the improvement of lung function, even after the oxygen therapy was discontinued.

Risk factors of mortality in meconium aspiration syndrome: review of 314 cases.

Meconium aspiration syndrome (MAS) is a common severe respiratory disease in full-term infants. To investigate the risk factors for mortality of MAS, a retrospective chart-review study of MAS was conducted from 1995 to 2001. All cases of MAS were included except cases of cyanotic congenital heart disease or congenital fetal anomaly. Prenatal, perinatal and postnatal risk factors of mortality were recorded. The risk factors were compared between surviving and deceased cases. There were 314 cases of MAS during the seven years. Total mortality rate was 4.8% (15/314); this did not change significantly during these years. Risk factors of mortality by univariate analysis were: outborn babies, resuscitation before admission, first born baby, low pH, high oxygen index (OI), high alveolar-arterial oxygen tension gradient (AaDO2) at admission, high OI and AaDO2 at 2 hours after admission, shock, pneumothorax, asphyxia, pulmonary hemorrhage, persistent pulmonary hypertension of newborn (PPHN), and renal failure. Logistic regression analysis showed asphyxia, pneumothorax and PPHN are the most important risk factors of mortality in MAS. How to diminish these events is the key point for reducing the mortality rate of MAS.

Outcome of vocal cord paralysis in infants.

Although laryngomalacia is the leading cause of stridor in infancy, vocal cord paralysis, despite its low incidence, is still the second most common cause. However, the etiology of infant vocal cord paralysis is different from that of adults, and the management protocol is controversial. Therefore, we conducted this study to better characterize the cause and outcome of vocal cord paralysis in infants. From January 1997 to December 2003, we treated thirteen infants younger than one year for vocal cord paralysis. Seven infants were idiopathic (idiopathic group), two might be caused by prior surgery (iatrogenic group), two might be caused by central neuropathy (neurological group), and two were born after difficult delivery (obstetrical group). In the idiopathic group, six infants spontaneously recovered and one infant had right-side recovery, but the left side was still paralytic. All infants in the iatrogenic and obstetrical groups spontaneously recovered. However, no infant in the neurological group recovered. Spontaneous recovery occurred in 76.9% of affected infants. More than half (70%) of these spontaneous recoveries occurred within 6 months. In our experience, direct flexible laryngoscopy is mandatory for all infants younger than one year of age presenting with stridor. Except for extreme infants (e. g. bilateral vocal cord paralysis with severe respiratory distress and central neuropathy) who require a temporary tracheotomy to relieve the airway obstruction, we recommend waiting for at least 6 months before proceeding to invasive surgical interventions.

No association of urokinase gene 3'-UTR polymorphism with bronchopulmonary dysplasia for ventilated preterm infants.

Pathological findings pertaining to bronchopulmonary dysplasia (BPD) are consistent with a process of prolonged lung inflammation and impaired healing. The balance of the competing activities of coagulation and fibrinolysis may contribute to the premature lung's response to acute injury. We investigated the association of the urokinase gene polymorphism with BPD in ventilated preterm infants whose gestational age was below 30 weeks. BPD is defined as infants remaining dependent upon active respiratory support and/or oxygen supplementation and featuring characteristic radiographic changes in the lung fields on the 28th postnatal day (BPD-28d) and at a corrected age of 36 weeks of gestation (BPD-36w). Two hundred and four ventilated preterm infants were enrolled in the study. The typing of each specific genotype polymorphism was performed by polymerase chain reaction (PCR) and restriction analysis. Perinatal risk factors for BPD, genotype distribution, and allelic frequencies were compared between infants suffering from BPD (28-d), BPD (36-w) and their respective ventilated preterm infants who did not develop BPD infants. The genotype proportions of the urokinase 3'-UTR polymorphism for BPD (28-d), BPD (36-w) and their respective ventilated preterm infants who did not develop BPD did not differ significantly. There was no difference in allelic frequency for the urokinase 3'-UTR polymorphism between BPD (28-d), BPD (36-w) and their respective ventilated preterm infants who did not develop BPD infants. We concluded that urokinase gene 3'-UTR C/T polymorphism is not a suitable marker for predicting susceptibility and severity to BPD for preterm infants of Taiwanese.

A comparison of survival in extremely low birth weight infants between periods 1997-1998 and 1998-2000.

The survival rates and the influential perinatal factors of extremely low birth weight (ELBW) infants were compared between two periods, including January 1997 through May 1998 (Period 1, n = 84) and June 1998 through December 2000 (Period 2, n = 145). The survival rate was 48.8% (41/84) during Period 1 and 55.2% (80/145) during Period 2. Gestational age (GA) and birth weight (BW) were the most important factors that influenced the survival rate. The cut off levels, below which mortality rates increased significantly, were GA < 24 weeks and BW < 700 gm during Period 1 and GA < 24 weeks and BW < 500 gm during Period 2. During Period 1, the smallest survival was a female infant with GA of 23 weeks and BW of 530 gm who had no complication and lived well. During Period 2, the smallest survival was a female infant with GA of 21 weeks and BW of 460 gm who was discharged with home oxygen therapy. She was admitted again via emergency due to sudden onset of apnea and cardiac arrest 4 days after discharge, and she died 4 days after the 2nd admission. Our results did not show any advantages to maternal transfer or delivery by Cesarean section. The early neonatal mortality rate was still high during Period 2 and accounted for 50% of the overall neonatal mortality rate. This implies that further training to improve the neonatal care, especially during the early stage of the first week should be reinforced to reduce neonatal deaths. Prevention of the births of extremely premature infants should be more emphasized to decrease neonatal mortality and morbidity rates. When the delivery of an ELBW infant is impending, an active plan of treatment for all infants of GA > or = 24 weeks or BW > or = 500 gm seems appropriate.

Clinical analysis of necrotizing enterocolitis with intestinal perforation in premature infants.

To identify the prognostic factors correlating with the outcome of the perforated necrotizing enterocolitis (NEC), the charts of 20 premature infants with perforated NEC were reviewed. Eight patients had long-term survival and 12 died. Infants in the survival group had significantly lower incidence of starting to feed before perforation, patent ductus arteriosus, indomethacin use, acidosis, and shock. Sepsis was only found in the group of infants that died The survival group were diagnosed with NEC and intestinal perforation at an earlier age than the infants that died. The time from diagnosis of NEC to intestinal perforation was longer in the infants that died. The localization of necrosis from operativefindings were all confined to the ileum-cecum area in survival group. The infants in the survival group were likely to have a single perforation. In addition, according to the operative management, they were divided into three groups: Group I consisted of six patients who received peritoneal drainage only, group II consisted of three patients who received peritoneal drainage followed by laparotomy, and group In consisted of 11 patients who received primary laparotomy. Infants in groups I and II had significantly lower gestational ages and birth weights than group III. There were no significant differences in mortality rates among infants in groups I, II and III. We concluded that the factors including prior enteral feeding, patent ductus arteriosus, indomethacin use, acidosis, sepsis, shock, delayed onset of NEC and perforation, multiple perforation, and diffuse necrotic changes were significant prognostic factors of poor outcome. Peritoneal drainage was a resuscitative procedure in critical condition and laparotomy should mostly be considered as the final treatment in the infants with perforated NEC.

Inhaled nitric oxide in persistent pulmonary hypertension of the newborn: four-year experience in a single medical center.

Forty-eight infants with persistent pulmonary hypertension of the newborn (PPHN) from July, 1997 to June, 2001 were enrolled for a prospectively study to determine the role of inhaled nitric oxide (NO) treatment and to determine an appropriate weaning strategy of NO. The initial dose of NO was started at 10 ppm for 10 minutes. If the infant's symptoms did not improve, we used a rapid dose ladder schedule for increasing the dose of NO to 20, 40 and 80 ppm every 10 minutes until we achieved the desired response. When oxygenation improved for 30 minutes, NO was decreased by 5 ppm every 10 minutes until reaching 5 ppm which was maintained for 2-3 hours. During the NO weaning period, if the SpO2 decreased by 10% or fell below 85%, the NO was increased to the previous higher dose and maintained this lowest effective dose for 2-3 hours. During this period, FiO2 was decreased by 10% every 10 minutes and peak inspiratory pressure was decreased gradually as the infant tolerable to avoid a decrease in saturation; we then tried to repeat the weaning procedure of NO. Inhaled NO was discontinued at 5 ppm if the infants were stable for 2-3 hours, and at the same time FiO2 was permitted to raise 10-20%. If SpO2 decreased by 10% or fell below 85% within 5 minutes, NO was reinstated at 5 ppm. A second attempt at weaning NO was made 2-3 hours later when the infants were stable. Thirty-four infants (70.8%) survived. Forty infants (83.3%), including 34 who survived and 6 who died, had good responses to inhaled NO. The mean effective NO concentration was 37 (5-80) ppm. The mean duration of inhaled NO treatment was 43 (6-153) hours. This study has demonstrated that inhaled NO is an effective rescue treatment for infants with severe PPHN, but the final outcome of infants depends not only on the response to inhaled NO but also on the associated complications. Using our weaning strategy, we shortened the duration of inhaled NO treatment as compared with a previous study (43 vs. 87 hours). Beginning inhaled NO therapy early in severe PPHN may be an important factor in shortening the duration of NO therapy. Further controlled trials of this weaning strategy are warranted.

Risk factors of extubation failure in extremely low birth weight infants: a five year retrospective analysis.

Extubation failure is one of the most serious complications in extremely low birth weight infants (ELBWI) on mechanical ventilation therapy. We performed a 5-year retrospective analysis to realize the status of extubation failure in ELBWI. Extubation failure was defined as requirements of re-intubation within 72 hours after extubation. The extubation failure rate was 21% (29/138). The mean birth body weight was 808.3 +/- 140.4 gm. The mean gestational age was 25.8 +/- 1.2 wks. The incidence of chronic lung disease (CLD) in infants with extubation failure was 100% (29/29). Apnea of prematurity 49% (14/29) and post-extubation atelectasis 39% (11/29) were the most common reasons for reintubation. The major microbiology findings which correlated with nosocomial pneumonia in infants with extubation failure were Acinetobacter baumanni (21%), Klebsiella pneumonia (21%), Pseudomonas aeroginosa (14%), and Methicillin resistant staphylococcus aureus (14%). In conclusion, post-extubation atelectasis and apnea were the most common reasons for reintubation. ELBWI with extubation failure had higher incidences of post-extubation atelectasis, CLD, and nosocomial pneumonia. Further prospective studies are needed in order to clarify the appropriate extubation program for ELBWI and to prevent post-extubation atelectasis and nosocomial pneumonia.