Tzong-Jin Wu

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life.

Background: Ventilation with higher PaCO2 goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO2 goal than in previous trials. Objective: To determine the clinical benefits and safety of higher PaCO2 goals for ventilated preterm infants. Study Design: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO2 target between 55 and 65 mm Hg (7.3– 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7– 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18–22 months corrected age. Results: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). Conclusion: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.

Persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) is a severe pulmonary disorder which occurs at a rate of one in every 500 live births. About 10-50% of the victims will die of the problem and 7-20% of the survivors develop long-term impairments such as hearing deficit, chronic lung disease, and intracranial bleed. Most adult survivors show evidence of augmented pulmonary vasoreactivity, suggesting a phenotypical change. Several animal models have been used to study the pathophysiology and help to develop new therapeutic modality for PPHN. The etiology of PPHN can be classified into three groups: (1) abnormally constricted pulmonary vasculature as a result of parenchymal diseases; (2) hypoplastic pulmonary vasculature; and (3) normal parenchyma with remodeled pulmonary vasculature. Impaired vasorelaxation of pulmonary artery and reduced blood vessel density in lungs are two characteristic findings in PPHN. Medical treatment includes sedation, oxygen, mechanical ventilation, vasorelaxants (inhaled nitric oxide, inhaled or intravenous prostacyclin, intravenous prostaglandin E1, magnesium sulfate), and inotropic agents. Phosphodiesterase inhibitors have recently been studied as another therapeutic agent for PPHN. Endothelin-1 (ET-1) inhibitors have been studied in animals and a case of premature infant with PPHN successfully treated with an ET-I inhibitor has been reported in the literature. Surfactants have been reported as an adjunct treatment for PPHN as a complication of meconium aspiration syndrome. Even with the introduction of several new therapeutic modalities there has been no significant change in survival rate. Extracorporeal membrane oxygenator is used when medical treatment fails and the patient is considered to have a recoverable cause of PPHN.

Transfusion-related acute lung injury treated with surfactant in a neonate

A term, male neonate suddenly developed respiratory distress and severe cyanosis while undergoing exchange transfusion for hyperbilribinaemia. Transfusion-related acute lung injury was diagnosed. Because of persistent hypoxaemia despite aggressive treatment, two doses of surfactant were administered, resulting in marked improvement.

Nitrotyrosine Impairs Angiogenesis and Uncouples eNOS Activity of Pulmonary Artery Endothelial Cells Isolated From Developing Sheep Lungs

Infection is known to impair the growth of developing lungs. It is known that plasma free nitrotyrosine (NT) levels can reach 150 μM during sepsis. Free NT incorporates into microtubules and impairs cell function. We hypothesize that free NT perturbs the angiogenic activity of pulmonary artery endothelial cells (PAEC) in developing lungs. PAEC from fetal lamb lungs were incubated with NT (1–100 μM). We examined the effects of NT on tube formation, cell proliferation, apoptosis, and α-tubulin assembly in PAEC. We assessed superoxide anion (O2−) and NO levels in PAEC during NT exposure. Effects of NT on endothelial NO synthase (eNOS) were examined with respect to eNOS-dimer formation and the association of eNOS chaperone, heat-shock-protein-90 (hsp90). NT decreased tube formation and increased apoptosis in PAEC. NT also decreased NO levels, increased NOS-dependent O2− generation, and promoted α-tubulin depolymerization. Although NT increased eNOS homodimer formation, it decreased the hsp90 association with eNOS. Our data suggest that increased NT formation during sepsis may uncouple eNOS activity and increase oxidative stress. Because NO plays an important role in angiogenesis and vasodilation, these observations suggest a mechanism for the impaired vasodilation and angiogenesis during sepsis in the developing lung.

Diffuse neonatal haemangiomatosis with intra-uterine haemorrhage and hydrops fetalis: a case reporte

A case of diffuse neonatal haemangiomatosis involving the skin, liver, lungs, adrenals, gums, diaphragm, skull, and testes is reported. Intra-uterine onset of bleeding led to bloody amniotic fluid, severe anaemia, congestive heart failure, and hydrops fetalis. Intractable coagulopathy and renal failure resulted in persistent bleeding, anuria, metabolic acidosis, and hyperkalaemia, leading to a fatal outcome.

Impaired Immune Function in a Premature Infant with Zinc Deficiency after Total Parenteral Nutrition

The report describes a premature infant with necrotizing enterocolitis who developed symptoms of zinc (Zn) deficiency after three to four weeks of total parenteral nutrition (TPN). Clinical presentations included characteristic skin rash, alopecia, retarded growth, generalized edema and decreased serum alkaline phosphatase (ALP). Immune function studies revealed impaired neutrophil adhesion and mitogen-induced lymphoproliferation, whereas phagocytosis, chemotaxis and lymphocyte subsets remained normal. A high dose of elemental Zn (2.5 mg/kg/day), administered orally, improved the clinical symptoms and restored the immune function. In patients with Zn deficiency, impaired neutrophil adhesion and lymphocyte function may contribute to immunodeficiency which can be reversed with adequate Zn supplementation.

Nonprogressive congenital unilateral ventriculomegaly

Congenital unilateral ventriculomegaly is a rare condition, usually caused by obstruction of the foramen of Monro. In the past, this condition required surgical intervention. We present a female newborn with nonprogressive unilateral ventriculomegaly which was initially detected by prenatal sonography. No surgical intervention was performed, and during the 9 months of follow-up, she had normal head growth and reached appropriate developmental milestones.

Risk factors of cholestasis in very low-birth-weight infants.

To evaluate the incidence, clinical course, and possible risk factors of cholestasis in very low-birth-weight infants. A retrospective study of 143 very low-birth-weight infants was performed. Cholestasis was defined as direct-reacting bilirubin > 2 mg/dL for more than 14 days. The clinical course of cholestasis was described, and perinatal risk factors were evaluated for associations with the development and severity of cholestasis. Cholestasis was present in 31 infants (21.7%). The mean (SD) age of onset was 30.3(15.3) days after birth or 26.0 (15.6) days after receiving parenteral nutrition, and the mean (SD) duration was 77.1 (33.8) days. In half of the cholestatic infants, bilirubin continued to rise after discontinuing parenteral nutrition. One infant developed signs of liver cirrhosis and died, two infants died with progressive cholestasis, while the other 28 patients recovered. Analysis of risk factors revealed that birthweight and duration of fasting significantly correlated with the development of cholestasis, and that sepsis significantly influenced the severity of cholestasis. Cholestasis is a common complication of extreme prematurity. The clinical course seems benign but long-term sequelae are unknown. Immature liver function and absence of stimuli for intestinal motility and hormonal secretion predispose to decreased bile flow, while sepsis further impairs hepatic ductular secretion and aggravates cholestasis.

Comparison of the outcome of extremely-low-birth-weight infants between two periods

A comparison was made of the outcome of 73 neonates born with their birth weight of 500-999 gm in National Taiwan University Hospital during the period between January 1, 1993 and December 31, 1996 (Period II), with the outcome of 21 such neonates born between April 1, 1988 and October 31, 1992 (Period I). Exclusion criteria included parental refusal for resuscitation, and major anomalies. Data were collected via a predetermined record sheet. The incidences of the extremely-low-birth-weight infants were 23/10,173 (0.23%) and 81/13,835 (0.59%) in Periods I and II, respectively. Early neonatal mortality rate was significant decreased in Period II (43% versus 14%). The limit of viability was improved from gestational age of 26 weeks or 700 gm to gestational age of 24 weeks or 600 gm. The incidence of neonatal morbidity (80% versus 50%) and total survival rate (48% versus 60%) have not changed significantly as seen in this limited number of cases. This study concluded that, with the introduction of exogenous surfactant and modern neonatal care, early neonatal survival rate and the limit of viability were improved.

Retinopathy of prematurity in very-low-birthweight neonates : Epidemiology and risk factors

A retrospective study of 143 very-low-birthweight infants cared in a level III neonatal intensive care unit who had survived for at least 28 days. Initial eye ground evaluation was done at the postnatal age between 4 and 6 weeks. Follow-up evaluation was done every one to two weeks at the discretion of the ophthalmologists. Thirty-four variables were reviewed for each case. Statistical analysis was done for each variable, with the development of retinopathy of prematurity (ROP), severity of ROP and development of threshold ROP as the dependent variables, by Mann-Whitney U test or X2 test when adequate. Variables with P-valu < 0.05 were included in multiple regression. One hundred and thirty-eight cases were survived for more than 28 days with their eyes been checked. Twenty-six (18.8%) of them developed ROP. The prevalence of stage I was 2.2% (3/138), stage II was 3.6% (5/138), stage III was 12.3% (17/138), and stage V was 0.7% (1/138). Threshold disease, stage 3 (+) and above, was found in 5 cases (3.6%). Seventeen variables were found to be correlated with the development of ROP. Only the duration of continuous positive airway pressure (CPAP) was significantly correlated to the development of ROP in multivariate logistic regression. Fifteen variables were correlated with the severity of ROP, but only peak direct bilirublin level, peak total bilirubin level and duration of CPAP could entered multiple stepwise linear regression. Thirteen variables were correlated with the development of threshold ROP, but only episodes of septicemia enter the multivariate logistic regression. We postulate that the longer duration of CPAP in ROP cases may reflect the severity of apnea and episodes of hypoxic attacks. Reducing episodes of apnea may prevent the development of ROP. The number of episodes of septicemia was the only significant variable for threshold ROP so that infection control is important for the prevention of threshold disease.