Neonatal outcomes of extremely preterm infants from taiwan: comparison with Canada, Japan, and the USA.

BACKGROUND: This study compared the current trend in survival rates and morbidity for very low birth weight (VLBW) infants in five Medical Training Centers of Prematurity for the Premature Baby Foundation of Taiwan (PBFT), with the outcomes from the USA, National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN), the Canadian Neonatal Network (CNN), and the Neonatal Research Network of Japan (NRNJ). METHODS: The survival rates of VLBW infants according to gestational age (GA) and major morbidities were compared between networks (Taiwan, USA, Canada, and Japan). Taiwanese data for VLBW infants of GA ≤28 weeks between 2007 and 2012 were obtained from the "PBFT Annual Conferences of Premature Care" reports defining survival rate as neonates that survived to the time of discharge. Major morbidities included severe neurological injury (Grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia), bronchopulmonary dysplasia, severe retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, and patent ductus arteriosus. RESULTS: The survival rates of VLBW infants of GA ≤28 weeks from the PBFT (Taiwan), NICHD NRN (USA), CNN (Canada), and NRNJ (Japan) were 77% (1323/1718), 72% (6859/9575), 82% (2353/2872), and 89% (4489/5069), respectively. The annual survival rates in Taiwan from 2007 to 2012 were 72%, 76%, 76%, 74%, 77%, and 78%, respectively. When GA from ≤23 weeks to 28 weeks was assessed in Taiwan, the survival rates of VLBW infants according to each week were 22%, 50%, 70%, 80%, 88%, and 92%, respectively. The survival rate, especially at lower GAs, was highest in the NRNJ (Japan). The major difference between Taiwan and Japan was attributed to the lower survival rates at lower GA (≤26 weeks) in Taiwan. Japan had the lowest rates of major morbidities among the four countries. CONCLUSION: The survival rate of VLBW infants has improved over the past 6 years in Taiwan. It is higher than the USA, but lower than Canada and Japan. However, the results from Taiwan are from five Medical Training Centers for the PBFT rather than from a population-based study. It is crucial to have a nationwide neonatal research network to develop new practical approaches for VLBW infants in Taiwan.

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).

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.

Nonassociation of interleukin 4 intron 3 and 590 promoter polymorphisms with bronchopulmonary dysplasia for ventilated preterm infants.

Interleukin 4 (IL-4) stimulates and amplifies the inflammatory response, stimulates collagen synthesis in fibroblasts, promotes the progression to fibrosis and has been shown to inhibit the production of several inflammatory cytokines in the development of bronchopulmonary dysplasia (BPD) and airway hyperreactivity. We aimed to investigate whether IL-4 polymorphisms in ventilated preterm infants were associated with BPD. BPD was defined as infants who remained dependent on active respiratory support or oxygen supplementation at 36 weeks postconceptional age. A case-control study of 224 preterm infants (<30 weeks) who had respiratory distress syndrome and needed intermittent mandatory ventilation (IMV) were undertaken between January 1999 and December 2003. The typing of each genetic polymorphism was performed by polymerase-chain-reaction-based restriction analysis. Genotype distribution and allelic frequencies were compared between ventilated preterm infants who developed BPD and those who did not and the duration of IMV. The demography of these ventilated BPD and non-BPD preterm infants was not different. We observed no significant differences in genotype distribution or allelic frequency of the IL-4 intron 3 or IL-4 promoter polymorphisms between ventilated preterm infants who developed BPD and who did not. There was no significant association of the genotype or allelic frequency of IL-4 polymorphism with duration of IMV. We conclude that neither IL-4 intron 3 nor the 590 promoter polymorphism is a useful marker for predicting the susceptibility to BPD in ventilated Taiwanese preterm infants.

No association between TAP1 DpnII polymorphism and bronchopulmonary dysplasia.

The possibility that a family history of asthma may have a role in susceptibility to bronchopulmonary dysplasia (BPD) had been raised in several reports, and there was evidence of a strong association between transporter associated with antigen processing (TAP1) polymorphism and asthma in Taiwanese population. To test whether TAP polymorphism has a role in the BPD, we investigated the association between TAP1 polymorphism and BPD by analyzing the results of genotype distribution. The study included 224 ventilated preterm infants (<30 weeks) who had respiratory distress syndrome (RDS) and needed intermittent mandatory ventilation (IMV) during Jan. 1999 to July 2003. The typing of TAP1 polymorphism was performed by polymerase chain reaction (PCR)-based restriction analysis. The demography between two groups of these ventilated preterm infants was not different. We observed no significant differences in genotype distribution or allele frequency of the TAPI polymorphisms between BPD and their respective control infants. There was also no significant difference in genotype distribution of the TAP1 polymorphism with duration of IMV. Therefor, we conclude that TAP1 polymorphism is not a useful marker for predicting the susceptibility or severity to BPD for Taiwanese.

Medical treatment with atropine sulfate for hypertrophic pyloric stenosis.

We investigated whether atropine sulfate was an effective, non-surgical method for treating hypertrophic pyloric stenosis (HPS). The study group consisted of 5 patients, all of the patients presented with projectile vomiting. Hypertrophic pyloric stenosis was diagnosed based on abdominal sonographic findings. The age when symptom arose was 30.8 +/- 15.5 (mean +/- SD) days, the age upon admission was 43.2 +/- 9.6 days. The frequency of vomiting was 5.8 +/- 2.3 times per day. After admission, all patients received 10% atropine sulfate 0.01 mg/kg intravenous (i.v.) for 5 minutes q4H (every four hours) before each feeding. Formular milk was started and increased by 10 ml every feeding until full feeding (120 ml/kg/day) was achieved. When vomiting had ceased for a period of one day, i.v. atropine was changed to 0.02 mg/kg oral q4H before each feeding. The patient was hospitalized until full feeding was maintained for more than 2 days. Then oral atropine was tapered by half a dose every 2 weeks. Oral atropine was continued until the thickness of the pyloric muscle had normalized (< 3.5 mm). All five patients were successfully treated with atropine sulfate. The frequency of vomiting was reduced to less than two times per day (1.8 +/- 1.3 days). i.v. atropine was used for 6.4 +/- 3.4 days, and the oral form was used for 30 +/- 9 days. The total number of days of atropine sulfate treatment was 36.4 +/- 9.58 days. Full feeding was achieved at 8 +/- 5.3 days. The hospitalization was 14.6 +/- 6.2 days. The body weight when admitted was 4000 +/- 760.8 gm and the body weight when discharged was 4282 +/- 901 gm. The body weight one month after treatment was 5210 +/- 772.5 gm. The body weight gain one month after atropine treatment was 1262 +/- 441.4 gm. Body weigh range on admission was from <3rd to 25th percentile, and after one month of atropine treatment, the body weight range was from 10th to 75th percentile. Complications included transiently elevated heart rates (180-200 times/min) in two patients and facial flushing after the first dose of IV atropine in one patient. In conclusion, conservative treatment with initially IV atropine in the initial stages instead of oral atropine sulfate is an effective alternative to pyloromyotomy, particularly in infants with major concurrent disease or when parents are unwilling to let their infants undergo surgery. Surgical intervention is not always necessary.

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.

Risk factors for retinopathy of prematurity in very low birth-weight infants.

PURPOSE: To calculate incidence and evaluate the risk factors of the threshold retinopathy of prematurity (ROP) in very low birth-weight (VLBW, birth weight less than 1,251 gram) infants. We also compared the incidence of threshold ROP in Taiwan with those of Caucasians and Negros. Additionally, the post-conception age when threshold ROP happened was considered. METHODS: From February 1995 to February 2000, we enrolled 458 VLBW infants at the China Medical College Hospital. Patients with congenital anomalies and those who survived less than 6 months were excluded. The perinatal and neonatal data of enrolled infants were reviewed. Student's t test and chi-square test were used to evaluate the statistical significance of risk factors. We also used logistic regression test and correct classification rate to evaluate different risk factors. RESULTS: The incidence of threshold ROP in our study was 6.8%. The gestational age (GA), birth weight (BW), number of days in using ventilator, continuous positive airway pressure (CPAP) and oxygen supplements, the occurrence of broncopulmonary dysplasia (BPD), respiratory distress syndrome (RDS), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) and the length of hospitalization were statistically different between patients groups with and without threshold ROP (p < 0.05). However, small size for gestational age (SGA), sepsis status, intraventricular hemorrhage (IVH) status (Gr.III and Gr.IV) and type of delivery were not significantly different between patients with and without threshold ROP (p > 0.05). Threshold ROP was noted at an average post-conception age of 34.25 weeks. CONCLUSIONS: The incidence of threshold ROP (6.8%) in VLBW Taiwan babies is comparable with the incidence of Caucasian patients in Western countries. Risk factors including PVL, NEC, BPD and RDS should be avoided to prevent the occurrence of threshold ROP. Threshold ROP occurred at an average of 34.3 weeks of post-conception age; the premature baby around this age must be checked carefully.

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.