Salivary cytokine - A non-invasive predictor for bronchopulmonary dysplasia in premature neonates.

BACKGROUND: To find a less invasive method of cytokine detection for premature neonates, we conducted this cohort study to investigate the salivary cytokines and to analyze their correlations with bronchopulmonary dysplasia (BPD). METHODS: Premature neonates younger than 34 weeks of gestational age without maternal or neonatal infection were recruited. Salivary samples were collected on their first (D1) and seventh (D7) days of life. The cytokine levels were detected by MILLPLEX® MAP Human multiplex assay. One-way analysis of variance, the Kruskal-Wallis test, Pearson's chi-square test, and logistic regression were used to analyze the data. RESULTS: Totally 125 neonates were enrolled and separated into four groups: control, mild, moderate, and severe BPD group. The salivary levels of D1 interleukin (IL)-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, and D7 IL-6 (p = 0.001, 0.001, 0.000, 0.043, 0.037 and 0.001, respectively) were significantly higher in the BPD groups than in the control group. After adjusting for the gestational age, acid-base equivalent, and absolute neutrophil count, comparing to the control group, the levels of D7 IL-17 became significantly lower in all three BPD groups (p = 0.032, 0.030, and 0.030, respectively) and that of D7 IFN-α2 became significantly lower in the severe BPD group (p = 0.037). CONCLUSION: Early-life salivary cytokine levels were correlated with the development of BPD in premature neonates. This study provides a novel method to predict BPD early and non-invasively.

Effects of maternal nicotine exposure on lung surfactant system in rats.

Maternal smoking during pregnancy may impair pulmonary function in infants and children, but the exact mechanisms underlying these changes remain to be determined. Timed pregnant Sprague-Dawley rats were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from days 3-21 of gestation. A control group was injected with saline. Nicotine-treated dams had lower body weights than control dams from gestational days 5-21, and the values reached statistical significance on gestational days 17, 20, and 21. Total lung saturated phosphatidylcholine contents tended to be lower in nicotine-exposed rats than in control rats from postnatal day 21, and the values reached statistical significance on postnatal days 35 and 42. Maternal nicotine exposure significantly increased surfactant protein (SP)-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 7, and decreased SP-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 14. In conclusion, maternal nicotine exposure during pregnancy reduces lung surfactant lipids and produces variable changes in surfactant protein gene expression during the late postnatal period. As good surface activity of pulmonary surfactant is essential for normal lung function, these results suggest that derangement of the pulmonary surfactant system may be important in the pathogenesis of impaired pulmonary function in children exposed in utero to nicotine.

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).

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.

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.

Cardiopulmonary manifestations of fulminant enterovirus 71 infection.

BACKGROUND: The pathogenesis of acute pulmonary edema and cardiac collapse after enterovirus 71 (EV71) infection are not completely understood. OBJECTIVE: To determine the hemodynamic features and the mechanism of pulmonary edema (PE) after EV71 infection by direct intracardiac monitoring. DESIGN: Prospective clinical and laboratory study at a tertiary medical center. PARTICIPANTS: Five consecutive infants, ages 2 to 13 months, with EV71 infection-proved by viral isolation in 4 and antibody in 1-with PE were enrolled. The clinical characteristics were systemically assessed. Hemodynamic profiles were determined every 4 hours by simultaneously implanted pulmonary arterial and central venous catheters during the acute stage. RESULTS: Magnetic resonance imaging revealed that all 5 infants had brainstem lesions. All patients had tachycardia and hyperthermia. Transient systolic hypertension was noted in 1 patient, and 1 presented with hypotension. Pulmonary artery pressure in all 5 infants was normal or mildly elevated (26-31 mm Hg), and central venous pressure ranged from 10 to 22 mm Hg. Pulmonary artery occlusion pressures were normal or slightly elevated (13-16 mm Hg). Systemic and pulmonary vascular resistances were transiently increased in only 1 patient. The stroke volume index decreased to 15.3 to 35.7 mL/M2 (normal: 30-60 mL/M2), but because of the elevated heart rate, the cardiac index did not decrease. All hemodynamics normalized within days. CONCLUSION: Fulminant EV71 infection may lead to severe neurologic complications and acute PE. The acute PE and cardiopulmonary decompensation in EV71 infection are not directly caused by viral myocarditis. The mechanism of PE may be related to increased pulmonary vascular permeability caused by brainstem lesions and/or systemic inflammatory response instead of increased pulmonary capillary hydrostatic pressure.