OBJECTIVETo detect potential mutation of COL2A1 gene in two children suspected for Kniest dysplasia.

METHODSThe 54 exons and splicing regions of the COL2A1 gene were amplified with PCR and the product was subjected to direct sequencing.

RESULTSA missense mutation (c.905C>T, p.Ala302Val) was found in the coding region of the COL2A1 gene, which has been previously reported in abroad. The patients appeared to have short trunk dwarfism, enlarged joints and midface hypoplasia.

CONCLUSIONThe probands are the first cases of Kniest dysplasia described in China, and so was the p.Ala302Val mutation.

Base Sequence ; Child, Preschool ; China ; Cleft Palate ; genetics ; Collagen Diseases ; genetics ; Collagen Type II ; genetics ; Dwarfism ; genetics ; Exons ; Face ; abnormalities ; Humans ; Hyaline Membrane Disease ; genetics ; Male ; Molecular Sequence Data ; Mutation, Missense ; Open Reading Frames ; Osteochondrodysplasias ; genetics ; RNA Splicing

The benefits of exogenous synthetic or animal-derived natural surfactants for treatment of respiratory distress syndrome (RDS) are well established. Although synthetic surfactants have potential safety advantages over animal-derived products, they seem to be clinically inferior to animal-derived natural surfactant, based on the results of numerous comparative trials. In recent years, however, synthetic surfactant has experienced a surge in breakthroughs to the point of rivaling natural surfactant, mainly due to the development of protein-containing synthetic surfactant. This article will review the historical background on the development of artificial pulmonary surfactant, compositional and physicochemical aspects on pulmonary surfactant lipids and proteins, results of comparative trials among natural, protein-free and protein-containing surfactants, and current status of development of protein-containing surfactants for treatment of RDS.
Humans ; Hyaline Membrane Disease ; Infant, Newborn ; Infant, Premature ; Proteins ; Pulmonary Surfactants ; Surface Tension ; Surface-Active Agents

OBJECTIVETo evaluate the effects of morphine infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in ventilated neonates.

METHODSA randomized, double-blind clinical trial was conducted between August 2010 and April 2011 at the neonatal intensive care unit of Nanjing Children's Hospital Affiliated to Nanjing Medical University. A total of 46 ventilated preterm infants (≥ 32 weeks) and term infants were divided into 2 groups at random. Twenty-two infants in test group received a loading dose (100 µg/kg) of morphine (> 1 h) followed by a continuous infusion [10 µg/(kg·h)] for (70.05 ± 29.05) h, and 24 infants in control group received 5% glucose with the same infusion rate. (1) The ventilatory parameters [respiratory rate (R), frequence (f), peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), fraction of inspired oxygen (FiO2)], mean blood pressure (MBP) and heart rate (HR) before treatment, at 30 min, 2 h, 6 h, 12 h, 24 h, 48 h after treatment between two groups were compared. (2) Pain was measured by two assessment tools [neonatal pain, agitation and sedation scale (N-PASS) and COMFORT scale] at the same periods. (3) The ventilation duration, the time from withdrawal to extubation, the total oxygen-inhaled time, the side effects and the clinical outcomes [e.g., pulmonary hemorrhage, air leak, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH)] between two groups were compared.

RESULTS(1) There were no significant differences in the different ventilatory parameters before and after treatment between two groups at different periods (P > 0.05). There was no significant difference in the average blood pressure of two groups at different periods, but the heart rate reduced at 24 - 48 h after treatment in test group with significant difference as compared to control group (t = -2.152 and -2.513, P < 0.05). (2) The N-PASS score and COMFORT score in test group were lower than that in control group at different time points 2 h after treatment (P < 0.05), especially 12 h after treatment (P < 0.01). (3) There were no significant differences in the ventilation duration, the time from withdrawal to extubation and the total oxygen time between two groups, and also in side effects, the incidence of IVH, white matter damage and the clinical outcomes.

CONCLUSIONContinuous infusion of morphine could relieve pain in ventilated neonates, reduce the stress response and promote the human-machine coordination, but the medication did not show any effects on neurobehavioral development and short term outcome.

Analgesics, Opioid ; administration & dosage ; pharmacology ; Double-Blind Method ; Female ; Humans ; Hyaline Membrane Disease ; therapy ; Infant, Newborn ; Infant, Premature ; Infusions, Intravenous ; Intensive Care Units, Neonatal ; Lung Diseases ; therapy ; Male ; Morphine ; administration & dosage ; pharmacology ; Pain ; drug therapy ; etiology ; Pain Measurement ; methods ; Respiration, Artificial ; adverse effects ; Treatment Outcome

PURPOSE: The objectives were to identify the characteristics of neonates with hydrops fetalis, and to identify the risk factors associated with mortality. METHODS: A retrospective review of AMC (Asan Medical Center) dataset was performed from January 1990 to June 2009. The characteristics of 71 patients with hydrops fetalis were investigated and they were divided into two groups: the survived group and the expired group. Various perinatal and neonatal factors in two groups were compared to find out risk factors associated with mortality based on univariate analysis, followed by multiple regression analyses (SPSS version 18.0). RESULTS: Of those 71 neonates (average gestational age: 33 weeks, birth weight: 2.6 kg), 38 survived, 33 died, resulting in overall mortality rate of 46.5%. The most common etiology was idiopathic followed by chylothorax, cardiac anomalies, twin-to-twin transfusion, meconium peritonitis, cardiac arrythmias, and congenital infections. Factors that were associated independently with mortality in logistic regression analyses were low 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days. CONCLUSION: In this study, 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days were significant risk factors associated with mortality in hydrops fetalis. Therefore, the risk of death among neonates with hydrops fetalis depends on the illness immediately after birth and severity of hydrops fetalis. Informations from this study may prove useful in prediction of prognosis to neonates with hydrops fetalis.
Apgar Score ; Arrhythmias, Cardiac ; Chylothorax ; Edema ; Gestational Age ; Humans ; Hyaline Membrane Disease ; Hydrops Fetalis ; Ideal Body Weight ; Infant, Newborn ; Logistic Models ; Meconium ; Parturition ; Peritonitis ; Prognosis ; Retrospective Studies ; Risk Factors

OBJECTIVEThis study examined the changes of serum levels of estradiol during the early postnatal period in neonates in order to investigate the possible relationship between the serum estradiol levels and the occurrence of pulmonary hyaline membrane disease (HMD) and bronchopulmonary dysplasia (BPD).

METHODSFifty-nine premature infants with the gestational age between 26 and 32 weeks and 61 full-term infants with the gestational ages between 37 and 42 weeks were enrolled. Serum levels of estradiol were measured on postnatal days 1, 3 and 7.

RESULTSSerum levels of estradiol decreased rapidly after birth in both premature and term infants and there were significant differences among different postnatal ages groups. However, there were no significant differences in the serum estradiol levels between the premature and term groups on postnatal days 1, 3 and 7. Serum estradiol levels measured in premature infants with HMD were not statistically different from those in premature infants without HMD on all time points. Serum estradiol levels in premature infants with BPD were higher than those in premature infants without BPD on postnatal day 3, but there were no noticeable differences on postnatal days 1 and 7.

CONCLUSIONSSerum estradiol levels decline rapidly within 7 days after birth in both premature and term infants. Serum estradiol levels in the early postnatal period are not associated with the occurrence of HMD and BPD, suggesting that serum estradiol in the early postnatal period can not be used as a marker for predicting the development of HMD and BPD.

Biomarkers ; Bronchopulmonary Dysplasia ; blood ; Estradiol ; blood ; Female ; Humans ; Hyaline Membrane Disease ; blood ; Infant, Newborn ; Male

This patient was born at 25th week of gestation with extremely low birth weight (700 grams) and hyaline membrane disease. On his 9th day as neonate, he was diagnosed to have a patent ductus arteriosus (PDA). Due to pulmonary congestion/ hypertension on top of failure of the said PDA to close after a regimen of ibuprofen and subsequently indomethacin, surgical intervention was contemplated which however was delayed because of the onset of pneumonia and bronchopulmonary dysplasia. On the 59th day of life, PDA ligation was done at the Nursery ICU. The patent weighted 800 grams at his supposed to be 33- 34 weeks age of gestation making him the smallest infant to be reported who have underwent PDA ligation in the Philippines.
Human ; DUCTUS ARTERIOSUS, PATENT ; INFANT, LOW BIRTH WEIGHT ; PREMATURE BIRTH ; INFANTS ; NEUROMUSCULAR BLOCKING AGENTS ; HYALINE MEMBRANE DISEASE ; LIGATION

OBJECTIVEInflammatory reaction and injury in immature lungs are associated with activation of nuclear factor-kappa B (NF-kappaB) to trigger proinflammatory cytokine release, but the mechanism thereof is not fully understood. The present study was conducted to understand possible relationship between expression of NF-kappaB and its inhibitor and severity and outcome of neonates with hyaline membrane disease (HMD).

METHODSSerial samples of bronchoalveolar lavage fluid (BALF) were obtained during mechanical ventilation from 31 preterm infants with HMD. These infants were divided into two groups: survivors group [n = 22, birth weight (1500 +/- 320) g and gestational age (31.2 +/- 1.8) weeks] and nonsurvivors group [birth weight (1340 +/- 280) g, gestational age (30.8 +/- 2.1) weeks]. Nineteen preterm infants [birth weight (1470 +/- 280) g, gestational age (30.6 +/- 1.9) weeks] without respiratory disorders were enrolled as control subjects. Alveolar macrophages (AM) were isolated by differential adherence. AM was cultured and treated with lipopolysaccharide (LPS) for 1 hr. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay (EMSA) for NF-kappaB expression. NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by using Western blotting and IL-1beta and IL-8 in BALF by enzyme-linked immunosorbent assay (ELISA).

RESULTSNF-kappaB complexes were observed by EMSA, they were characterized by competition with cold oligonucleotide and p65-specific antibodies. The addition of an excess of cold oligonucleotide, corresponding to the NF-kappaB binding site, turned off the signal of the band, showing that the band was specific. An excess of an irrelevant oligonucleotide (corresponding to the SP-1) did not show any effect. The addition of an anti-p65 antibody caused the supershift of the two upper bands. After EMSA, the NF-kappaB complexes were quantified by using a ImageQuant software. NF-kappaB expression in AM at 24 hrs was higher in all the patients with HMD as compared with control subjects (survives/control, 34.1 vs 11.4 RDU, P < 0.01; nonsurvivors/control, 55.2 vs 11.4 RDU, P < 0.01). The NF-kappaB expression in AM at 72 hrs was higher than that in control subjects but not for nonsurvivors (survivors/control, 47.8 vs 25.6 RDU, P < 0.01; nonsurvivors/control, 21.8 vs 25.6, P > 0.05). The NF-kappaB expression in AM from nonsurvivors was depressed at 72 hrs as compared to 24 hrs (21.8 vs 55.2, P < 0.01), whereas the NF-kappaB expression in AM from survivors was still higher at 72 hrs than that at 24 hrs (47.8 vs 34.1, t = 4.43, P < 0.01).

CONCLUSIONAltered NF-kappaB activation in AM of BALF of neonates with HMD was observed, and it may be mediated by decreased IkappaB synthesis, increased IkappaB degradation, or both. In HMD nonsurvivors NF-kappaB translocation was hampered upon LPS activation.

Birth Weight ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; cytology ; Cell Culture Techniques ; Cell Nucleus ; drug effects ; metabolism ; Cytoplasm ; drug effects ; metabolism ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Female ; Gestational Age ; Humans ; Hyaline Membrane Disease ; immunology ; therapy ; I-kappa B Proteins ; immunology ; Infant, Newborn ; Infant, Premature ; immunology ; Interleukin-1beta ; immunology ; Interleukin-8 ; immunology ; Lipopolysaccharides ; pharmacology ; Macrophages, Alveolar ; drug effects ; immunology ; Male ; NF-KappaB Inhibitor alpha ; NF-kappa B ; immunology ; Respiration, Artificial ; Severity of Illness Index ; Time Factors

PURPOSE: To compare the efficacy of conventional strategy versus high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for the treatment of full term neonates with persistent pulmonary hypertension (PPHN). METHODS: Full term infants admitted with diagnosis of PPHN to neonatal intensive care units of Asan Medical Center from a period of 1994 to 2001 were included. The major exclusion criteria included congenital anomalies and pulmonary hypoplasia caused by various etiologies. Demographic, therapeutic responses and outcomes were compared between two study phases depending upon treatment modalities used: phase 1 (January 1994-July 1997) using conventional strategy and phase II (July 1997-December 2001) using either conventional strategy or/with iNO or HFOV with iNO. RESULTS: A total of 16 patients and 32 patients were enrolled in phase I and phase II studies, respectively. The primary diagnosis for PPHN included idiopathic (n=12), hyaline membrane disease (n=16), meconium aspiration syndrome (n=11), and sepsis (n=10). Statistically significant improvements were noted in survival, oxygenation index and alveolar- arterial oxygen tension difference during phase II than phase I study period. 75% of those infants treated with iNO showed good responses. Improvements in duration of ventilator use, oxygen supplementation, hospitalization were noted during phase II study period, however, not statistically significant compared to phase I study period. The impairments in neurodevelopmental outcomes were noted in 1 and 2 patients during phase I and phase II study periods, respectively. CONCLUSION: We conclude that HFOV and iNO are more efficacious and safe rescue mode of treatment than conventional strategy for full term infants with PPHN.
Chungcheongnam-do ; Diagnosis ; Hospitalization ; Humans ; Hyaline Membrane Disease ; Hypertension, Pulmonary* ; Infant ; Infant, Newborn* ; Intensive Care Units, Neonatal ; Meconium Aspiration Syndrome ; Nitric Oxide ; Oxygen ; Sepsis ; Ventilation ; Ventilators, Mechanical

PURPOSE: This study is to evaluate the clinical significance and possible etiologies of abnormal neurosonographic findings that revealed linear or branching linear hyperechoic vascular lesions in the thalami and basal ganglia of neonates and infants. METHODS: Analysis of 2,866 cranial sonograms (US) and doppler ultrasonography obtained from 1,150 patients identified 53 patients with linear hyperechoic vascular lesions in the thalami or basal ganglia. Patients with only punctate or coarse, nonlinear lesions of echogenicity in these lesions were excluded. Clinical records in 53 patients were reviewed for documentation of congenital cytomegalovirus (CMV) infection, rubella, syphilis, toxoplasmosis, chromosomal abnormality and other major diagnoses. Brain computed tomography (CT) had been performed in 23 of the 53 patients and these images were compared with the cranial sonograms. RESULTS: There were five CMV infection, two congenital syphilis, three Down syndrome, and one Patau syndrome patients. Other major diagnoses encountered included perinatal asphyxia, ventriculomegaly, intraventricular hemorrhage, periventricular leukomalacia, small-for-gestational age, prematurity with hyaline membrane disease, multiple congenital anomalies, neonatal seizure, meningitis, congenital choroid plexus cyst, neonatal hyperbilirubinemia, congenital heart disease, bronchopulmonary dysplasia and others. Brain CT found small calcification in basal ganglia from one patient. Resolution of lesions found in 5 cases with follow-up US studies. CONCLUSION: A broad etiologic basis for linear hyperechoic vascular lesions in the thalami and basal ganglia of neonates and infants indicates complete screening for possible various etiologies.
Asphyxia ; Basal Ganglia* ; Brain ; Bronchopulmonary Dysplasia ; Choroid Plexus ; Chromosome Aberrations ; Cytomegalovirus ; Diagnosis ; Down Syndrome ; Follow-Up Studies ; Heart Defects, Congenital ; Hemorrhage ; Humans ; Hyaline Membrane Disease ; Hyperbilirubinemia, Neonatal ; Infant ; Infant, Newborn* ; Leukomalacia, Periventricular ; Mass Screening ; Meningitis ; Rubella ; Seizures ; Syphilis ; Syphilis, Congenital ; Toxoplasmosis ; Ultrasonography* ; Ultrasonography, Doppler

OBJECTIVE: To compare the perinatal outcomes in twin and singletone pregnancies delivered prematurely between 28 and 36 weeks gestational age. METHODS: We studied 80 pairs of twin delivered between 28 weeks and 36 weeks gestational age at Eulji university hospital between January 1996 and October 2000. The perinatal morbidity and mortality in premature twin pregnancies were compared to those of premature singleton pregnancies (N=402). RESULTS: The premature twin pregnancies had no significant differences of gestational age at delivery than those of singleton pregnancies, but significantly lower mean birth weight. In mean day of hospital stay, 1 and 5 min Apgar scores, there were no significant differences. There were no significant differences in the incidence of neonatal morbidity such as hyaline membrane disease, and retinopathy of prematurity, between the two groups. And also the perinatal mortality was not significantly different between the two groups. CONCLUSION: There were no significant differences in perinatal mortality and morbidity between the two groups.
Birth Weight ; Gestational Age* ; Humans ; Hyaline Membrane Disease ; Incidence ; Infant, Newborn ; Length of Stay ; Mortality ; Perinatal Mortality ; Pregnancy* ; Pregnancy, Twin ; Retinopathy of Prematurity