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Background Chronic pulmonary obstructive disease (COPD) has become the fourth leading cause of death worldwide. Cigarette smoking induces neutrophil elastase (NE) and contributes to COPD, but the detailed mechanisms involved are not fully established. In an animal model of pulmonary emphysema, there are increased expressions of placenta growth factor (PlGF) and lung epithelial (LE) cell apoptosis. This study hypothesized that excessive NE may up-regulate PlGF and that PlGF-induced LE apoptosis mediates the pathogenesis of pulmonary emphysema. Methods Human bronchial epithelial cells, BEAS-2B, and primary mouse type II alveolar epithelial cells were treated with NE. The PlGF promoter activity was examined by luciferase activity assay, while PlGF expression and secretion were evaluated by RT-PCR, Western blotting, and ELISA. Both cell lines were treated with PlGF to evaluate its effects and the downstream signaling pathways leading to LE cell apoptosis. PlGF knockout and wild-type mice were instilled with NE to determine the roles of PlGF and its downstream molecules in NE-promoted mice pulmonary apoptosis and emphysema phenotype. Results The transcriptional factor, early growth response gene-1, was involved in the NE-promoted PlGF promoter activity, and the expression and secretion of PlGF mRNA and protein in LE cells. PlGF-induced LE cell apoptosis and NE-induced mice pulmonary apoptosis and emphysema were mediated by the downstream c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)δ signaling pathways. Conclusion The NE-PlGF-JNK/PKCδ pathway contributes to the pathogenesis of LE cell apoptosis and emphysema. PlGF and its downstream signaling molecules may be potential therapeutic targets for COPD. Electronic supplementary material The online version of this article (doi:10.1186/s12931-014-0106-1) contains supplementary material, which is available to authorized users.

Background A rotavirus outbreak in a neonatal intensive care unit (NICU) may have catastrophic consequences for young infants receiving critical care. From May 13, 2011 to July 11, 2011, a significant increase in stool samples testing positive for rotavirus antigens in the NICU of a university affiliated hospital was observed. Due to lack of clinical presentations suggestive of rotavirus infection in the patients and the rarity of rotavirus infection in the NICU in the past, a pseudo-outbreak was suspected. Methods Infection control measures were reinforced initially. To investigate the outbreak, a prospective laboratory-based active surveillance of all infants in the NICU was conducted right after the cluster was identified. Repeated testing using a modified enzyme immunoassay (EIA) kit, rotavirus RNA polyacrylamide gel electrophoresis (PAGE), reverse transcription polymerase chain reaction (RT-PCR), and retrospective chart review methods were used to confirm the pseudo-outbreak. Results Seven infants in the NICU, with or without gastrointestinal symptoms, tested positive for the rotavirus antigen using the old version of an EIA kit, which indicated a possible outbreak. Active surveillance with repeated tests for recollected stool samples using a modified EIA kit showed negative results in all 24 infants in the NICU. Seven stored stool samples from four infants, which previously tested positive for the rotavirus antigen, tested negative for rotavirus using the modified EIA kit, PAGE, and RT-PCR. Chart reviews showed no clinical difference between index cases and controls. False positivity might arise from unsatisfactory specificity of the old EIA kit. After the introduction of the modified EIA kit, no rotavirus was detected in the NICU for at least 7 months. Conclusion This cluster of patients who tested positive for the rotavirus antigen in stools was confirmed to be a pseudo-outbreak. Interpretation of the old EIA for rotavirus in an NICU setting should be done with caution until the mechanism of the false-positive reaction is elucidated.

Background Most neonates who reside in the neonatal intensive care unit (NICU) and require surgery are transferred to the operating room (OR) or undergo bedside surgery. However, critically ill neonates who are transferred often encounter the risk of complications. An OR in our NICU was therefore launched in 2009. This study was to appraise the surgeries performed in the NICU OR and compare results with the traditional main OR outside the NICU. Methods This was a retrospective study in the NICU of a tertiary center. Retrospective chart review was conducted for all neonates who underwent surgical procedures in the NICU OR and the main OR. The information regarding baseline characteristics, surgical procedures and duration, ventilator use, hypothermia, hyperglycemia, instrument dislocations, surgically related infection or complications, and outcomes was obtained. Results There were a total of 65 patients in this study, 37 in the NCIU OR group and 28 in the main OR group. The presurgical mean airway pressure and the fraction of inspired oxygen (FiO 2 ) were comparable between the two groups, but the postsurgical FiO 2 was significantly lower in the NICU OR group (31.0%) than in the main OR group (40.9%; p = 0.027). Furthermore, the NICU OR group required a significantly shorter preoperation waiting time (34.4 minutes vs. 63.6 minutes, p = 0.001) and had a lower incidence of hypothermia than the main OR group (8.1% vs. 39.3%, p = 0.008). However, surgically related complications were similar between groups. Conclusion The OR within the NICU may reduce the risk of complications during transportation and provide continuity of care to critically ill neonates. It also decreases the disturbance to other NICU patients during operation.

Agenesis of the corpus callosum is the most common brain malformation. It may be an isolated malformation or a component of a malformation syndrome. Associated Central Nervous System (CNS) and non-CNS malformations have been broadly reviewed. However, the coexistence of a large ocular lipodermoid has never been mentioned. We reported a female newborn with multiple congenital anomalies, including complete agenesis of the corpus callosum with intracranial midline lipoma, a large epibulbar lipodermoid over the entire left cornea and a large Ventricular Septal Defect (VSD). No clinical neurological or cardiac symptoms or signs were noted during admission. She received an ocular tumor excision with amniotic membrane transplantation on the left eye at 10 days old. Limbal dermoids/lipodermoids are hallmarks of Goldenhar syndrome; however, our patient did not have preauricular tag, microtia, or vertebral anomalies. In addition, a chromosome study and comparative genomic hybridization array in this patient revealed no significant abnormalities. To the best of our knowledge, this is the first report of a case with a combination of agenesis of the corpus callosum, an ocular lipodermoid, and VSD.

Percutaneously inserted central venous lines are usually a safe and effective means of securing prolonged central venous access but can have serious complications. One patient who experienced clinically important morbidity related to inadvertent malpositioning of a central venous catheter is described. It was inserted via the left saphenous vein into the lumbar venous plexus and resulted in milky cerebrospinal fluid, urine retention, and paraplegia. Reviewing the literature, only 11 patients with the same malposition were reported, three of them with percutaneously inserted central venous lines. In these three patients and our patient the left saphenous vein was used. Neurologic sequelae of paraplegia and urine retention were recorded in 25% (3/12) of patients. The mortality rate approached 42% (5/12) but only two patients were related to catheter misplacement. Although the complication rate is extremely low and difficult to recognize, catheter malposition into the ascending lumbar vein can lead to lethal complications.

A fetus with a huge hepatic tumor was detected by sonography at 36 weeks of gestation. The mass appeared as a single, solid and polylobular tumor located in the right lobe of the liver. Foci of hemorrhage, necrosis and some tiny calcifications were seen. The adjacent right kidney appeared normal but was displaced. The right adrenal gland was not visualized. Three-dimensional power Doppler sonography further depicted the corresponding vascular anatomy of the tumor, including its vascularization pattern and blood supply. The tumor was situated to the right of the umbilical vein and portal sinus, possibly deriving its blood supply from the portal circulation. The fundamental findings suggested the diagnosis of hepatoblastoma by exclusion of other possibilities. The baby was delivered by Cesarean section at 36 weeks' gestation, due to signs of fetal distress. Unfortunately, hypotension, tachycardia, and tachypnea developed shortly after birth. Surgical intervention was performed, but intractable bleeding occurred intra-operatively. The infant died at 6 days of age. Autopsy confirmed the diagnosis of hepatoblastoma. We believe this is the first reported case of the antenatal diagnosis of congenital hepatoblastoma.

Neonatal sinus thrombosis is a rare occurrence in sick neonates. Because of its nonspecific manifestations, the incidence is underestimated. This disease may not be demonstrated by conventional color Doppler and is diagnosed by computed tomography or magnetic resonance imaging. The authors report a neonate with neonatal sinus thrombosis diagnosed by power Doppler and suggest that the technique may be used as a less expensive and more available screening and follow-up method in high-risk neonates.

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic congenital vascular anomaly characterised by persistent cutis marmorata, telangiectasia, and phlebectasia. The disease usually has a benign clinical course and over 50% of cases recover spontaneously without specific treatment. The occurrence of life-threatening complications in CMTC is rare. Conclusion:We report a neonate with life-threatening cutis marmorata telangiectatica congenita which was complicated by gangrenous ulceration, bleeding episodes, and hypovolaemic shock.

Background: Previous reports showed that prenatal hypoxia delays the process of lung maturation. Vascular endothelial growth factor (VEGF) and its receptors were important for lung development. However, the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia remains unknown. Objectives: To elucidate the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia. Methods: Lung sections of control and maternal hypoxic fetal mice were used for the determination of lung development and total RNA isolated from lung homogenates were used for determination of the expression patterns of VEGF, Flt-1, Flk-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, surfactant protein (SP)-A, SP-B, SP-C, and SP-D by quantitative real-time RT-PCR. Results: Prenatal hypoxia resulted in fetal mice body weight gain impairment, delayed fetal pulmonary aeration and maturation. Pulmonary SP-A, SP-B, SP-C, and SP-D mRNA were all decreased in the prenatal hypoxia group. In addition, we demonstrated that prenatal hypoxia inhibited the developmental increase of pulmonary HIF-1α and HIF-2α expression and resulted in decreasing VEGF and its receptors (Flt-1 and Flk-1) at the mRNA expression level and VEGF protein level in fetal lungs. These inhibitory effects persisted and progressed even when the dams were returned to air. Conclusions: We suggest that prenatal hypoxia insults, at least in late gestation, influence pulmonary VEGF and VEGF receptor expression through the down-regulation of HIF pathways and impair fetal lung growth and maturation.

Background Placenta growth factor (PlGF), a dimeric glycoprotein with 53% homology to VEGF, binds to VEGF receptor-1 (Flt-1), but not to VEGF receptor-2 (Flk-1), and may function by modulating VEGF activity. We previously have showed that PlGF displays prognostic value in colorectal cancer (CRC) but the mechanism remains elucidated. Results Overexpression of PlGF increased the invasive/migration ability and decreased apoptosis in CRC cells showing Flt-1 expression. Increased migration was associated with increasing MMP9 via p38 MAPK activation. Tumors grew faster, larger; with higher vascularity from PlGF over-expression cells in xenograft assay. In two independent human CRC tissue cohorts, PlGF, MMP9, and Flt-1 expressions were higher in the advanced than the localized disease group. PlGF expression correlated with MMP9, and Flt-1 expression. CRC patients with high PlGF and high Flt-1 expression in tissue had poor prognosis. Conclusion PlGF/Flt-1 signaling plays an important role in CRC progression, blocking PlGF/Flt-1 signaling maybe an alternative therapy for CRC.

BACKGROUND: Because environmental insults and genetic factors account for the variance in the risk of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW, birth weight < 1,500 g) preterm infants, the search for BPD biomarkers has begun to focus on the regulators of non-coding RNA such as microRNAs (miRNAs). Therefore, this study aimed to identify potential miRNAs involved in the pathogenesis of BPD in VLBW preterm infants. METHODS: A case-control study (15 subjects with BPD and 15 sex-matched control subjects without BPD) was conducted to investigate the expression profiles of 365 miRNAs in the peripheral blood of VLBW preterm infants at 36 weeks post-menstrual age (called the older-age set). The expression levels of identified miRNAs were further evaluated in a subsample of blood collected during the first 2 weeks post-natal age (called the younger-age set). Possible biological functions and pathways implicated in the target genes regulated by the miRNAs were explored using database predictions. RESULTS: A 4-miRNA signature ( miR-152 , miR-30a-3p , miR-133b , and miR-7 ) with aberrant expression levels at 36 weeks, derived from a supervised classification with internal cross-validation, discriminated the subjects with BPD from those without BPD with an accuracy of 0.91. The discriminative accuracy of the 4 miRNAs was supported by random permutations of either the disease status or the number of miRNAs selected (both P < .001). A down-regulation change of miR-152 and miR-30a-3p expression levels and an up-regulation change of miR-133b and miR-7 expression levels were found in the older-age set, compared to the younger-age set. CONCLUSIONS: This is the first study to identify blood-based miRNAs associated with BPD. The findings provide information regarding the roles of these biomarkers in the development of BPD in VLBW preterm infants.

BackgroundPreeclampsia remains a leading cause of maternal mortality and preterm delivery. Both preeclampsia and bronchopulmonary dysplasia (BPD) of prematurity are associated with impaired angiogenesis. However, the relationship between maternal preeclampsia and BPD remains controversial. This study aims to test whether or not preeclampsia is associated with development of BPD in a cohort of premature infants.Materials and methodsWe conducted a retrospective cohort study assessing the association between preeclampsia and the risk of developing BPD in very-low-birth-weight (VLBW) infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2006. All 21 neonatal departments in Taiwan participated in the data collection. A total of 8,653 VLBW infants were registered in the database. The exclusion criteria included congenital anomalies, chromosome anomalies, infants that died before 36 weeks post-conceptual (PCA), and those whose BPD status were unavailable. BPD was defined as oxygen dependence at 36 weeks postmenstrual age. The association between maternal preeclampsia and BPD was assessed using a multivariate-adjusted logistic regression model.ResultsIn the end, a total of 5,753 cases were enrolled in this study. The incidence of preeclampsia was 14.7% (n=847) and the overall incidence of BPD was 34.9%. Infants with maternal preeclampsia had a higher gestational age, higher incidence of cesarean section and being small for their gestational age, lower incidence of respiratory distress syndrome, patent ductus arteriosus, and sepsis. BPD occurred significantly less frequently in the maternal preeclampsia group (24.1% vs. 36.7%; adjusted odds ratio: 0.78; 95% confidence interval, 0.62-0.98). Subgroup analysis showed that the association between preeclampsia and BPD was significant only in those VLBW infants with a gestational age between 31-34 weeks.ConclusionThis data supports the association between fetal exposure to maternal preeclampsia and a reduced risk of BPD in relatively mature VLBW infants.

Midline cranial defects can be divided into lesions with intracranial tissue herniation (cranium bifidum cysticum) and lesions mainly with ossification failure (cranium bifidum occultum). Herniated cephaloceles mostly require surgical resection, while persisted parietal foramina might become smaller with age.Here, we report a neonate with large symmetric midline skull defect at high parietal area. A mild bulging mass was noticed. Interestingly, unlike sac herniation, it was surrounded by bony ridges extended from the rim of the calvarial defect, which suggests aberrant ossification. Persistent falcine sinus was also detected. At the corrected age of 11 months, the size of the skull defect had decreased spontaneously, favoring the diagnosis of parietal bone ossification defect. Potential mechanisms resulting in the special appearance of skull bone were discussed.Incomplete closing of the parietal foramina might be expected due to the aberrant ridge formation. We suggest protective measures for the calvarial defect.

Central retinal vein occlusion and intracerebral hemorrhage are rare diseases during infancy and are both related to venous thrombosis. We present the case of a full-term male hydrops infant without specific neurologic symptoms initially but later demonstrating bilateral central retinal vein occlusion and intracerebral hemorrhage. We conclude that routine funduscopic examination in high-risk newborns should be seriously considered.

A fast reversed-phase liquid chromatography- electrospray ionization triple quadrupole mass spectrometry method was developed for the molecular species profiling of glycerophosphocholine (GPC) and sphingomyelin (SM) in total lipid extracts. A two-stage mass spectrometry strategy was adopted to analyze in detail the composition of lipid molecular species. Precursor ion analysis was first con- ducted to obtain the preliminary composition profile of the phosphorylcholine-containing lipid. The product ion spectra were sequentially acquired for each recorded signal to de- termine the molecular structure of the lipid. A total of 150 GPCs and 12 SMs were identified in the fetal mouse lung with relative amounts ranging from 13.7 % to less than 0.002 % (normalizing by the total signal response). A col- umn packed with core-shell particles was used to obtain excellent chromatographic separation with a shorter time demand in a conventional high-performance liquid chroma- tography system. Considering the compromise between the chromatographic efficiency and the electrospray signal re- sponse, the optimization of the mobile phase improves the chromatographic plate number to approximately 40,000 and the detection limits to less than 0.001 mg/L. The applicabil- ity of the method was validated through a study of chemi- cally induced early lung maturation. The metabolic alteration in the fetal mouse lung was clearly reflected in the GPC and SM composition with several characteristics of the molecular structure that related to the character of the phospholipid layer upon the epithelial lining of alveoli and the relevant cell function. The results indicated that this analytical strategy is reliable for comprehensive molecular species profiling of GPC and SM and might be extended to the analysis of other phospholipids.

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

Anderson disease, also known as glycogen storage disease type IV (MIM 232500), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme. Glycogen storage disease type IV has a broad clinical spectrum ranging from a perinatal lethal form to a nonprogressive later-onset disease in adults. Here, we report 2 unrelated infants who were born small for their gestational age and who had profound hypotonia at birth and thus needed mechanical ventilation. Both of these patients shared the same frameshift mutation (c.288delA, pGly97GlufsX46) in the GBE1 gene. In addition, both of these patients were found to have 2 different large deletions in the GBE1 gene; exon 7 and exons 2 to 7, respectively, on the other alleles. This case report also highlights the need for a more comprehensive search for large deletion mutations associated with glycogen storage disease type IV, especially if routine GBE1 gene sequencing results are equivocal.

Goblet cell metaplasia and mucus overproduction contribute to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). Notch signaling regulates cell fate decisions and is crucial in controlling goblet cell differentiation in the gut epithelium. Little is known, however, about how endogenous Notch signaling influences the goblet cell differentiation program that takes place in the postnatal lung. Using a combination of genetic and in vitro approaches here we provide evidence of a novel role for Notch in restricting goblet cell differentiation in the airway epithelium during the postnatal period. Conditional inactivation of the essential Notch pathway component Pofut1 (protein O-fucosyltransferase1) in Tgfb3-Cre-expressing mice resulted in an aberrant postnatal airway phenotype characterized by marked goblet cell metaplasia, decreased Clara cell number and increase in ciliated cells. The presence of the same phenotype in mice in which the Notch transcriptional effector Rbpjk was deleted indicated the involvement of the canonical Notch pathway. Lineage study in vivo suggested that goblet cells originated from a subpopulation of Clara cells largely present in proximal airways in which Notch was disrupted. The phenotype was confirmed by a panel of goblet cell markers, showed no changes in cell proliferation or altered expression of proinflammatory cytokines and was associated with significant downregulation of the bHLH transcriptional repressor Hes5. Luciferase reporter analysis suggested that Notch directly repressed MUC5AC transcription in lung epithelial cells. The data suggested that during postnatal life Notch is required to prevent Clara cells from differentiating into goblet cells.

A strategy consisting of a two-phase analytical procedure was used to obtain detailed molecular species composition for glycerophosphocholines (GPCs) profiling in biological tissue using ultra performance liquid chromatography coupled with a triple quadrupole mass spectrometer operating under electrospray mode. In phase one of the analytical procedure, the precursor ion scan was first conducted to obtain the preliminary lipid profile that revealed the composition of the molecular species possessing phosphocholine structure in the biological tissue. In phase two of the analytical procedure, each product ion spectrum obtained for the GPC components in the profile was sequentially acquired for the determination of the molecular structure. A simple guide with high differentiability was proposed for the diacyl-, alkyl-acyl- and alk-1-enyl-acyl-GPC, and related lyso-GPCs molecular structure decision. Total 93 GPCs molecular species were identified in the fetal mouse lung with the relative amounts from 14.39% to less than 0.01% (normalizing by the total GPCs signal). The optimized chromatographic conditions were also proposed in the analytical procedure based on the compromise between the separation efficiency and electrospray signal response. The plate number of the probing GPCs was obviously improved to above 30,000 and the detection limits of the probing GPCs were between 0.002 and 0.016 ng/μL. The practical usability of the analytical procedure has been validated using a study of chemically induced early lung maturation. The metabolic difference between chemically treated and untreated fetal mouse lung was clearly distinguished by the composition of GPCs with several characteristics of molecular structure. The overall results showed that this two-phase analytical procedure was reliable for comprehensive GPC profiling.

Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS.

Osteopaenia commonly occurs in preterm infants; however, its diagnosis is often delayed when based on radiological findings. The aim of this study was to examine whether serial measurements of bone turnover markers are useful for early prediction of osteopaenia in preterm infants.Premature infants of ≤ 34 weeks gestation were enrolled. Serum alkaline phosphatase (ALP), bone form ALP (BALP), calcium and inorganic phosphate were concurrently measured biweekly from 3 weeks post-natal age until 40 weeks post-conceptional age. Radiographic examination of the forearm was performed at term age. Osteopaenia was defined as positive radiographic findings according to Koo's criteria.Of the 46 premature infants completing the follow-up study at term age, 18 showed osteopaenia in radiographic examination. Serum ALP was highly correlated with BALP (R(2) = 0.93, P0.001). Infants who had osteopaenia showed a higher level of ALP and BALP after 3 weeks post-natal age than those who had no osteopaenia. ALP concentration exceeding 700 IU/L at 3 weeks post-natal age was predictive of osteopaenia at term age (sensitivity 73% and specificity 73%) and so did for the predictive value of BALP concentration exceeding 95 ug/L (sensitivity 73% and specificity 80%). BALP measures provided no greater benefit of diagnostic performance than ALP in early detection of osteopaenia. Furthermore, premature infants with osteopaenia showed similar levels of calcium and inorganic phosphatase concentration compared with those without.Serum ALP concentration exceeding 700 IU/L at 3 weeks post-natal age can predict the risk of osteopaenia in preterm infants.

Breastfeeding jaundice is a common problem in neonates who were exclusively breastfed, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. We prospectively enrolled 688 near-term and term infants who were exclusively breastfed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than WTs (GG). This phenomenon was only seen in BF group but not in SF group when subset analysis was performed. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.

Background Patients with congenital duodenal obstruction (CDO) predominantly have a postampullary lesion site and a high association with Down syndrome, according to previous reports from Western countries. This study aimed to determine whether there are racial differences in the clinical characteristics of congenital duodenal obstruction, based on the experience from a Taiwanese medical center. Methods The charts were retrospectively reviewed among neonates with CDO who received surgery at National Taiwan University Hospital during the period 1985- 2008. Patients were grouped into a preampullary or postampullary group according to the obstruction in relation to the ampulla of Vater. Other characteristics, including sex, time of diagnosis, operative findings, as well as associated anomalies, were recorded for further analysis. Results A total of 30 patients with CDO including 16 with atresia, 10 with mucosal webs, and 4 with stenosis, were recruited; among them, 16 were boys and 14 were girls. In 15 patients (50%), the diagnosis of duodenal obstruction was made prenatally. A total of 11 of the 30 patients (37%) were in the preampullary group and 19 (63%) were in the postampullary group. Seventeen patients (56.7%) had at least one additional anomaly, including four (13%) who had trisomy 21. The preampullary group had significantly fewer associated congenital anomalies than in the postampullary group (27% vs. 74%, p = 0.012). Conclusion Our cohort showed a relatively lower incidence of postampullary lesions and associated Down syndrome in patients with CDO compared with Western countries. Additionally, patients with preampullary lesions had significantly less association with other anomalies.

Congenital intracranial teratoma is a rare disease. A fetus with a congenital intracranial teratoma presenting with a disproportionately enlarged head at 27 weeks gestation is presented. Prenatal ultrasonography and fetal magnetic resonance imaging demonstrate a huge, heterogenous intracranial mass in the left supratentorial region, with the left cerebral hemisphere being compressed and flattened. The infant died of respiratory failure within 24 hours of birth at 28 weeks gestation. On postmortem examination the histologic report revealed an immature teratoma. Fetal MRI is helpful in the prenatal diagnosis and evaluation of intracranial tumor.

Bronchopulmonary dysplasia (BPD) and very low birth weight (VLBW) are associated with increased incidences of asthma and pulmonary dysfunction in childhood. However, no studies exist which examine asthma risk factors in children who were VLBW infants and did not have BPD. To address this issue, we assessed the asthma incidence and risk factors for asthma in 117 children (approximate mean age of 5 years) who were VLBW [

PURPOSE: Increased angiogenesis at the site of the primary tumor in colorectal cancer has been associated with poor prognosis and relapse of disease. We previously demonstrated that the tissue level of placenta growth factor expression was upregulated in colorectal cancer and correlated with disease progression and patient survival. The aims of this study are to examine the prognostic value of serum placenta growth factor, vascular endothelial growth factor, and sFlt-1 and to compare them with the carcinoembryonic antigen levels in patients with colorectal cancer. METHODS: Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results. RESULTS: Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively. CONCLUSIONS: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.

Background Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental anomalies. Early surgical excision is becoming an increasingly common option. We investigated the clinical features and management of patients with CCAM and BPS at the National Taiwan University Hospital. Methods We conducted a retrospective review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995 to January 2008. Prenatal examination, postnatal presentation, management and patient outcome were analyzed. We also propose a concise algorithm for the practical management of these conditions. Results Sixteen patients were recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%) with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed antenatally at a median gestational age of 20 weeks. Eleven (69%) patients underwent surgical resection before 6 months of age because of respiratory distress or repeated pulmonary infection. There were no surgery-related complications among the seven patients who underwent early surgery within 1 month of age. Five (31%) patients remained asymptomatic and did not undergo surgery. All patients survived with no limitations to daily activity during follow-up periods of 1–8 years. Conclusion The high proportion of mixed-type lesions suggests that CCAM and BPS may share the same developmental ancestry. Early surgical resection within 1 month of age is safe in symptomatic patients.

Although there is accumulated evidence of a role for Notch in the developing lung, it is still unclear how disruption of Notch signaling affects lung progenitor cell fate and differentiation events in the airway epithelium. To address this issue, we inactivated Notch signaling conditionally in the endoderm using a Shh-Cre deleter mouse line and mice carrying floxed alleles of the Pofut1 gene, which encodes an O-fucosyltransferase essential for Notch-ligand binding. We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling. Strikingly, these mutants showed an almost identical lung phenotype characterized by an absence of secretory Clara cells without evidence of cell death, and showed airways populated essentially by ciliated cells, with an increase in neuroendocrine cells. This phenotype could be further replicated in cultured wild-type lungs by disrupting Notch signaling with a gamma-secretase inhibitor. Our data suggest that Notch acts when commitment to a ciliated or non-ciliated cell fate occurs in proximal progenitors, silencing the ciliated program in the cells that will continue to expand and differentiate into secretory cells. This mechanism may be crucial to define the balance of differentiated cell profiles in different generations of the developing airways. It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease.

Aim: Reference ranges of haematological parameters in preterm infants are limited. The aim of this study is to determine the reference values of haematological parameters in preterm infants in Taiwan, and to assess the impact of gestational age and mode of delivery on these parameters. Method: Medical records were retrospectively reviewed in preterm infants admitted to National Taiwan University Hospital from January 2001 to December 2004. The inclusion criteria included infants with

In vitro activation of macrophages by LPS induces rapid release of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 receptor (sFlt-1), which are thought to be the effectors to cause sepsis. However, the signal pathway that controls the VEGF and sFlt-1 expressions in LPS-activated macrophages remains unclear. In this study, we demonstrated that phosphorylation of protein kinase C (PKC)δ played a key role in the VEGF and sFlt-1 signaling pathway of LPS-activated macrophages. PKC is a family of serine-threonine kinases, which are classified into three major groups based on homology and cofactor requirements: conventional PKCs, novel PKCs, and atypical PKCs. In the murine RAW264.7 cells, as well as in primary human monocytes/macrophages, pretreatment with a general PKC inhibitor GF109203X or with a novel PKCδ inhibitor rottlerin or overexpression of a kinase-inactive form of PKCδ (K376R) eliminated LPS-induced sFlt-1 expression and augmented LPS-induced VEGF expression at the protein and the transcription levels. In contrast, Gö6976, an inhibitor for the conventional PKCs, or myristoylated PKCζ pseudosubstrate peptide, an inhibitor for the atypical PKCs, failed to exert the same effects. These data suggest that PKCδ signaling is involved in LPS-induced sFlt-1 expression and serves as a negative mediator in LPS-induced VEGF expression in macrophages. A novel strategy controlling the LPS-induced PKC pathways, especially the PKCδ isoform, may be developed based on this study.

Summary Objectives Listeria monocytogenes is an important pathogen in neonates in Western countries, with a fatality rate of 20–30%. There is limited information on neonatal listeriosis in Eastern countries. The purpose of this study was to delineate the occurrence and clinical picture of neonatal listeriosis in Taiwan. Methods A questionnaire-based survey of all of the 17 medical centers in Taiwan was performed, and a literature review of neonatal listeriosis as reported in Taiwan from 1990 to 2007 was made. Results A total of 14 cases (10 male, four female) of neonatal listeriosis were identified, including 11 found from the survey of four medical centers and another three collected from the literature review. Three were found to have occurred prior to 2000 and 11 were found to have occurred after 2000. The age of onset was less than 3 days in all cases. L. monocytogenes was identified from blood in 13, cerebrospinal fluid in four, and gastric aspirate in two. Half of the cases (7/14) had involvement of the central nervous system with pleocytosis and hypoglycorrhachia in cerebrospinal fluid, and three of them even developed hydrocephalus. The mortality rate was 29%. Conclusions Our findings suggest that listeriosis may emerge as an important health threat among newborn infants in Taiwan.

Complicated pneumonia, including necrotizing pneumonia, lung abscess, and empyema, caused by Streptococcus pneumoniae in children has been increasing. We thus determined to investigate its virulence in an animal model and to identify virulence factors of S. pneumoniae.Prospective, randomized, controlled animal study.University medical laboratory.Male Balb/c-strain mice, 3 wks old.We used a young mouse model to monitor bacterial virulence and a microarray to compare gene expression between S. pneumoniae from children with complicated and noncomplicated pneumonia. Deletion and complementation of a candidate gene were performed to study its role on the virulence of S. pneumoniae.A model of complicated pneumonia in young mice infected with strains of S. pneumoniae from children with complicated pneumonia was established. Using a microarray analysis, differences in zinc metalloprotease B (zmpB) RNA hybridization between two strains from children with complicated pneumonia (NTUH-p28 and NTUH-p15) and a strain (NTUH-p3) from a child with pneumococcal lobar pneumonia were found. Confirmatory assays revealed the signal differences were due to sequence variation in the zmpB gene. Infection with the zmpB deletion mutant of NTUH-p15 showed a significant decrease in the severity of pneumonia and no destructive lung injury. The zmpB complementation strain of NTUH-p15 significantly restored the level of inflammation and caused lung necrosis. For studying the effect of allelic variation of zmpB on the virulence of S. pneumoniae, we added zmpB of NTUH-p15 in the zmpB deletion mutant of NTUH-p3, which resulted in a higher bacterial burden than that in wild-type NTUH-p3.A young mouse model is established for complicated pneumococcal pneumonia. This model proved that allelic variation of zmpB affects the virulence of S. pneumoniae.

This study examined the developmental and clinical outcomes in very-low-birthweight (VLBW; < or =1500g) infants with and without bronchopulmonary dysplasia (BPD) throughout infancy, and assessed if BPD predicted poor developmental outcome beyond the effects of other risk factors. One hundred and three VLBW infants (53 males, 50 females; mean gestational age 28wks [SD 2] birthweight 1041g [SD 261]) were graded for severity of BPD according to the American National Institutes of Health (NIH) consensus definition. Neuro-development was assessed using the Neonatal Neurobehavioral Examination-Chinese version, at 36 and 39 weeks' postmenstrual age, and the 2nd edition of the Bayley Scales of Infant Development at 6 and 12 months' corrected age. Clinical outcome was measured by means of rehospitalization for pulmonary causes and treatment with pulmonary medications. Compared with infants without BPD, infants with BPD had higher rates of clinical morbidity, and those with severe BPD further exhibited higher incidences of developmental delay throughout infancy. BPD predicts poor 1-year developmental and clinical outcomes in VLBW infants for which effects are well correlated to the NIH consensus definition.

The aim was to determine the outcome and hospital cost for infants weighing

Congenital central hypoventilation syndrome (CCHS) is a rare neurological disorder characterized by abnormal autonomic central nervous system control of breathing during sleep. Mutations in the paired-like homeobox 2B (PHOX2B) gene, including point mutation, frameshift, and polyalanine expansion, are associated with the pathogenesis of CCHS. In this study, PHOX2B mutations were analyzed in seven CCHS patients, their family members, and 1520 healthy individuals from the general population using CE to provide high sensitivity and resolution screening for the PHOX2B polyalanine polymorphism. Seven mutations in the PHOX2B gene, including two frameshift mutations and five polyalanine expansions in the 20-residue polyalanine tract, were identified. The various phenotypes observed in CCHS patients with PHOX2B mutations suggest that the size of the expansion allele is associated with the CCHS risk. In addition, significant differences were found in allele and genotype distributions between the healthy individuals. Alleles (GCN)(20) and (GCN)(15) had the highest population incidence rates of 94.84 and 4.51%, respectively, with the remaining alleles, (GCN)(13) and (GCN)(7), accounting for 0.59 and 0.06%, respectively. Therefore, it has been demonstrated that CE can be used to improve the detection of polyalanine expansions in the PHOX2B gene. The attractive alternative method is a promising tool for the detection of disorders involving trinucleotide repeat tracts.

Preeclampsia and retinopathy of prematurity (ROP) are associated with impaired angiogenesis. Previous studies on the relationship between preeclampsia and ROP have produced conflicting results. The goal of this study was to evaluate the association between maternal preeclampsia and ROP using a large population-based cohort of very-low-birth-weight (VLBW) infants from 21 neonatal departments registered in the database of the Premature Baby Foundation of Taiwan. Multivariable logistic regression analysis was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for preeclampsia with reference to ROP and severe ROP. A total of 5,718 VLBW infants (844 cases with maternal preeclampsia) were included for analysis. The overall incidences of mild and severe ROP were 36.0% and 12.2%, respectively. Univariable analysis showed lower GA and lower birth weight, vaginal delivery, non-SGA, RDS, PDA, sepsis, transfusion, and absence of maternal preeclampsia to be associated with mild and severe ROP development. However, OR (95% CI) adjusted for the variables that were significant according to univariable analysis showed the risks of developing any-stage ROP and severe ROP for maternal preeclampsia to be 1.00 (0.84-1.20) and 0.89 (0.63-1.25), respectively. The results remained unchanged in stratified analyses according to SGA status. Our data showed that maternal preeclampsia was not associated with the subsequent development of any stage or severe ROP in VLBW infants.

Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway epithelium injury in mice. Repeated exposure of mice to naphthalene induces airway epithelia that are resistant to further injury. Previous studies revealed that alterations in bioactivation enzymes and increased levels of gamma-glutamylcysteine synthase in the bronchioles protect tolerant mice from naphthalene and its reactive metabolites. In our current study, tolerance was induced in male ICR mice using a total of 7 daily intraperitoneal injections of naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate metabolite differences. The lungs, liver, and kidneys were collected for histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid (BALF) and both hydrophilic and hydrophobic extracts from each organ were analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The histological results showed no observable injuries to the airway epithelium of naphthalene-tolerant mice when compared with the control. In contrast, airway injuries were observed in mice given a single challenge dose (injury mice). The metabolomics analysis revealed that the energy metabolism in the lungs of tolerant and injury mice was significantly perturbed. However, antioxidant metabolites, such as glutathione and succinate, were significantly increased in the lungs of tolerant mice, suggesting a role for these compounds in the protection of organs from naphthalene-induced electrophilic metabolites and free radicals. Damage to the airway cellular membrane, as shown by histopathological results and increased acetone in the BALF and perturbation of hydrophobic lung extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty acyl chains, were observed in injury mice. Consistent with our histopathological results, fewer metabolic effects were observed in the liver and kidney of mice after naphthalene treatments. In conclusion, NMR-based metabolomics reveals possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in the respiratory system of mice.

We report on a neonate with a huge congenital hemangioma of the scalp presenting as high-output heart failure and Kasabach-Merritt syndrome. The condition was successfully treated by means of surgical excision. A prematurely born (gestational age=36 weeks; birth weight=2,316 g), three-day-old female infant was referred to our institution for a huge scalp tumor (Fig. 1), already detected by fetal ultrasonography at six months of gestation. Head computed tomography scan revealed a hypervascular tumor of the scalp with strong heterogeneous enhancement. Magnetic resonance imaging demonstrated multiple feeding arteries, mainly consisting of an anastomosis of bilateral superficial temporal arteries and branches of the internal carotid artery. There was no evidence of intracranial hemorrhage. The patient had early heart failure signs including progressive respiratory distress and tachycardia. A small patent ductus arteriosus was present (1.2 mm in size). Thrombocytopenia (134 10/L) on the 1st day of life progressed to the lowest level (107 10/L) on day 3. On day 4, normocytic anemia (hemoglobin=11.5 g/dL) was present, prothrombin time was prolonged (16.3 seconds) as was partial thromboplastin time (79 seconds). Direct Coombs_ test was negative and both fibrin split products (80–160 mg/ml; normal

Hemangiopericytoma is a rare malignant vascular tumor that usually occurs in adults. The occurrence of these tumors in infants, known as congenital or infantile hemangiopericytoma, is even rarer and their behavior may be more benign than the adult type. We describe a 1-day-old female neonate with congenital hemangiopericytoma, presenting with a right inguinal mass at birth. At the time of surgery, lymphangio-ma was suspected because of its appearance, fluid-filled multicystic content, and the high incidence of this disease in pediatric patients. Tumor excision was performed and hemangiopericytoma was diagnosed by histology. There was no tumor recurrence during 12 months of follow-up.

Vein of Galen aneurysmal malformation (VGAM) often leads to death in the neonatal period, mainly due to congestive heart failure. Chronic and excessive pulmonary flow in utero and postnatally is attributed to large VGAM and right ventricular overload. We report a male neonate with VGAM complicated by severe heart failure and persistent pulmonary hypertension. Endovascular coil embolization of VGAM was performed, resulting in improvement of congestive heart failure; however, severe persistent pulmonary hypertension led to death 2 days after the embolization. Postmortem examination showed marked right and left ventricular hypertrophy and impressive muscular thickening of intra-alveolar arterioles. Neonatal embolization seems to be beneficial only in babies without suprasystemic pulmonary hypertension. Therefore, early delivery and repair of VGAM should be considered before the onset of persistent pulmonary hypertension.

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 non-progressive 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.

Objective To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC). Study design A retrospective study of all VLBW infants with PNAC who were admitted to a tertiary referral center was conducted. Patients were classified as treatment group (receiving UDCA within 14 days after onset of cholestasis) or control group (no medical treatment). Patients who received abdominal surgery were excluded. Results A total of 30 patients were recruited, including 12 in the treatment group and 18 in the control group. The demographic data, total fasting duration, onset of cholestasis, age to tolerance of full feeds, and the duration of parenteral nutrition (PN) before the onset of cholestasis were comparable between the two groups. There was a trend in the control group to later onset of cholestasis. The patients who received UDCA therapy with doses of 10 to 30 mg/kg/day had a shorter duration of cholestasis than the control group (62.8 vs 92.4 days, P = .006). Furthermore, the peak serum levels of direct bilirubin also was significantly lower in the treatment group. Conclusion UDCA can improve the course of PNAC in VLBW infants.

The adenomatous polyposis coli (APC) and mismatch repair (MMR) pathways are both involved in the tumorigenesis of hereditary colorectal cancers. Chemoprevention focuses on the APC pathway in the absence of information concerning MMR targets. This study compared the anticancer effects of sulindac, celecoxib, curcumin, and nifedipine in MMR-deficient cell lines, in order to determine the most appropriate chemopreventive agent for long-term use in patients with hereditary colorectal cancer.Five human colorectal cell lines (SW480, HCT116, LoVo, SW48, and HCT15) and an endometrial cancer cell line (HEC-1-A) were used for susceptibility testing. Tests included assays for growth inhibition, cell-cycle arrest, and apoptosis.Sulindac, celecoxib, curcumin, and nifedipine all displayed dose- and time-dependent anti-proliferation activities. Celecoxib was the most effective anti-proliferative agent, and increased the G0/G1 phase proportion in the cell cycle after treatment more significantly than the other agents in all cell lines. Curcumin displayed a more potent apoptosis-inducing activity than the other agents in treated cells.The tested drugs were effective against colorectal and endometrial cancer cell lines. Celecoxib is more potent with fewer side effects than sulindac. Nifedipine's observed chemopreventive efficacy may complement its known therapeutic application in patients with hypertension.

The incidence of trisomy 18 in monozygotic twins is approximately 1 per million. We report a pair of liveborn monozygotic twins with trisomy 18. Both twins had esophageal atresia with tracheoesophageal fistula (type C) and intrauterine growth retardation. Twin A had cleft lip, choanal atresia and perimembranous ventricular septal defect. Twin B had hypoplastic left heart syndrome. The twins died without aggressive intervention at the age of 2 months and 52 hours, respectively. These 2 babies had significantly discordant phenotypes, which suggests an epigenetic or environmental effect. Bioethical considerations remain important in the care of babies with multiple congenital anomalies.

Several lines of evidence suggest that angiogenesis is necessary for alveolarization and that inhibition of vascular growth during a critical period of early growth may impair alveolarization. However, little is known about the role of angiogenic factors during alveolarization. This study investigated the expression patterns of the Ang-Tie-2 family of endothelium-specific receptor tyrosine kinases and vascular endothelial growth factors and their receptors (VEGF-VEGFR system) during postnatal mouse lung development.The lungs from 3 or 4 mice from groups aged 3, 7, 10 and 14 days and adults were removed and dissected from the main bronchi for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Semi-quantitative RT-PCR of mouse lung total RNA was used to measure the expression levels of these angiogenic factors and their receptors.During alveolarization, VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 were up-regulated and PlGF/Flt-1 was kept at a relatively constant level. After alveolarization was completed, PlGF was down-regulated, Flt-1 was up-regulated, and VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 were maintained at relatively high levels.During alveolarization, in mice, VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 are up-regulated and PlGF/ Flt-1 is kept at relatively constant level to promote pulmonary microvascular development. In the adult mouse lung, when most of the vascular network is complete, PlGF is down-regulated and Flt-1 is up-regulated to stop angiogenesis and VEGF/Flk-1, Ang-1, Ang-2 and Tie-2 are kept at relatively high levels to maintain mature pulmonary microvasculature.

Advances in obstetrical and neonatal care have increased the survival of very-low-birth-weight (VLBW) infants, defined as infants weighingor = 1,500 g at birth, in many populations. To understand the morbidity and survival of VLBW infants in Taiwan, the records of all VLBW admitted to the 12 hospitals with a level II+ or level III neonatal intensive care unit (NICU), at7 days of age, from January 1 to December 31, 1996, were collected prospectively. A total of 613 VLBW infants (292 males and 301 females) met the enrollment criteria: 305 cases from the northern region, 181 cases from the central region, and 127 cases from the southern region of Taiwan. The mean birth weight was 1,133 g (range, 368-1,500); the mean gestational age (GA) was 28.9 weeks (range, 21-38). Among the VLBW infants, 25.8% were small-for-gestational-age, 90.2% were born to mothers with high-risk factor(s) for preterm delivery, 55% were born by cesarean section, and 68.1% required resuscitation at birth. The percentage of prenatal use of steroids was 52.9%, and20% received more than one dose of antenatal steroids. Thirty-three percent were born after antenatal maternal transfer, and the neonatal transfer rate was 23%. The most common neonatal complication was apnea of prematurity (66.1%), followed by respiratory distress syndrome (RDS) (60%). Chronic lung disease occurred in 76 cases (16.5%). The overall survival rate of the 613 VLBW infants was 76.2%; for infants weighingor = 1000 g at birth, it was 49.2%, and for infants weighing 1,001-1,500 g at birth, it was 88.5%. The survival rate for infants with a GAor = 26 weeks was 35.3%, and for infants with a GA of 27-36 weeks was 87.5%. No infant with a birth weightor = 600 g or a GA23 weeks survived. The most common cause of death was sepsis, followed by extreme prematurity (GAor = 23 wks) and RDS. Several perinatal and neonatal factors were related to the mortality. Multiple regression analysis of survival showed that GAor = 26 weeks, birth weightor = 800 g, delivery room resuscitation and the occurrence of pneumothorax were related to mortality. Therefore, although the survival rate of VLBW infants admitted to level II(+)-III NICUs showed an improvement over the rate for the previous 20 years in Taiwan, perinatal and neonatal care of extremely preterm infants and neonatal resuscitation programs need to be emphasized to improve the outcome of VLBW infants furthermore.

The objective of this study is to compare the neurodevelopmental outcome between very low birth weight infants with and without sonographic disproportionate enlargement of occipital horn. We retrospectively reviewed the brain sonography of all very low birth weight infants born at National Taiwan University Hospital between June 1997 and June 1999. Brain sonography was routinely performed at the age of the third, seventh, twenty-first, and later days as clinically indicated. Intracranial hemorrhage, periventricular leukomalacia, congenital hydrocephalus, and Stage III retinopathy of prematurity were excluded from our study because of the association with neurodevelopmental impairment. Patients with disproportional dilatation of occipital horn more than 15 mm in width were included in the study group, and those with less than 15 mm were in the control group. Both groups received developmental evaluation by the Bayley Scales of Infant Development II at corrected age of 6, 12, 18, and 24 months, respectively. Socioeconomic status and detailed medical history were obtained at assessments. Independent-samples t test was used for comparison. A total of 81 very low birth weight infants were included in this study: 49 infants (female 18, male 31) in the study group and 32 infants (female 23, male 9) in the control group. The mean gestation in these two groups was 30 +/- 2 weeks and 31.1 +/- 2.2 weeks (P = 0.156), and the mean birth body weight was 1290 +/- 269 gm and 1282 +/- 219 gm (P = 0.877), respectively. At corrected age of 24 months, there was no significant difference in muscle tone, neuromotor impairment, hearing impairment, vision, or speech development. Assessment with the mental development index (88.9 +/- 15.6 vs 93 +/- 13.2) (P = 0.238) and the psychomotor development index (93.3 +/- 10.3 vs 89.6 +/- 12.1) (P = 0.149) between these two groups was also comparable. This retrospective analysis suggests that ultrasonographic disproportionate enlargement of the occipital horn in very low birth weight infants does not affect the neuromotor development at corrected ages of 6, 12, 18, and 24 months.

Background and objective : In the literature, there are conflicting data on the neonatal outcome in preterm infants who were delivered for maternal pre-eclampsia. The purpose of this study is to investigate the effect of maternal pre-eclampsia on neonatal morbidity and 2-year developmental outcome in a population of preterm infants delivered before 32 weeks of gestation. Methods : The hospital records of all 89 surviving VLBW infants with GA below 32 weeks born from January 1997 to December 1999 were reviewed retrospectively. Data on respiratory outcome, sepsis and intraventricular hemorrhage (IVH) were compiled and analyzed for their association to maternal pre-eclampsia. Seventy-eight infants were assessed employing the Bayley Scales of Infant Development for developmental outcome at 2 years of corrected age. Results : There was no difference in neonatal morbidity between groups. More infants born to pre-eclamptic mothers had lower MDI scores at 24 months of age ( P =0.04) as compared to infants without maternal pre-eclampsia. After multiple logistic regression analysis, pre-eclampsia ( P =0.007, OR=10.8) remained a significant risk factor of mildly delayed MDI at 24 months of age. Conclusion : Delivery before 32 weeks because of pre-eclampsia was associated with an increased risk of poor cognitive outcome. There was no significant difference in the postnatal course in comparison with infants born after pregnancies not complicated by pre-eclampsia.

Hypercalcemia is occasionally found in newborns with subcutaneous fat necrosis and carries potential life-threatening risk. Bisphosphonates have been recently introduced in the treatment of subcutaneous fat necrosis in newborns. We report a case of extensive subcutaneous fat necrosis in a female infant complicated with intractable hypercalcemia. Standard treatment for hypercalcemia was given, including saline hydration, a low calcium diet, furosemide, and glucocorticoid, but without response. Serum 1,25-dihydroxyvitamin D level was elevated at 126 pg/mL, 25-hydroxyvitamin D level was normal, and intact parathyroid hormone was suppressed at1 pg/mL. Oral clodronate disodium, a second-generation bisphosphonate, was administered, and resulted in the normalization of serum calcium, urine N-telopeptide, urine calcium/creatinine ratio, and serum intact parathyroid hormone level. This case suggests that oral clodronate may be an effective treatment for subcutaneous fat necrosis with hypercalcemia in newborns.

Objective To describe a family on whom it was possible to perform a rapid prenatal diagnosis for chronic granulomatous disease (CGD) using a denaturing high-performance liquid chromatography (DHPLC) system. Methods For a family whose first-born, a boy, suffered from X-linked chronic granulomatous disease, fetal DNA was obtained from an ongoing pregnancy by amniocentesis early in the second trimester. Denaturing high-performance liquid chromatography and direct sequencing were used to attempt to detect the previously identified X-linked chronic granulomatous disease mutation. Results Our studies predicted that the fetus in question was not likely to be affected by chronic granulomatous disease, which was demonstrated to be correct at birth. Conclusions Here, we introduce a molecular diagnostic tool (DHPLC) for an effective and exact prenatal diagnosis of normality for the second-born child, as determined from amniocentesis during the second trimester. Copyright © 2003 John Wiley & Sons, Ltd.