The impact of small-for-gestational-age Status on the outcomes in very-Low-birth-weight (VLBW) premature infants: a prospective cohort study in Taiwan.

Background: The impact of small-for-gestational-age (SGA) on very-low-birth-weight (VLBW) premature infants remains inconclusive. This study aimed to assess the effects of being born SGA status on the short-term and long-term outcomes in VLBW preterm infants. Methods: We conducted a population-based, prospective cohort study on VLBW preterm infants born in Taiwan between 2012 and 2017. Sociodemographic, neonatal, growth and neurological data at 2 years of corrected age were collected. A total of 4243 VLBW infants born at 24 through 32 completed weeks' gestation participated in this study, of whom 1,005 had SGA status defined as a birth weight <10th percentile of gestation, and 3,238 did not (the non-SGA group).We compared the risks of short-term outcomes (neonatal mortality and morbidities), long-term outcomes (growth status, including weight, height, and head circumference <10th percentile, and neurodevelopmental impairments at 2 years of age). Subgroup analysis was performed by stratification of gestation age (GA): GA 24-26, 27-29 and 30-32 weeks. Results: In the analysis of short-term outcomes, the SGA group had an increased risk of neonatal mortality [adjusted odds ratio (OR) = 2.66, 2.99, and 2.19, respectively] in all GA subgroups in comparison with the non-SGA group (p < 0.05). The SGA group had a significantly increased risk of bronchopulmonary dysplasia in GA 27-29 and 30-32 weeks (adjusted OR = 2.11 and 1.86, respectively). We also found that there was an increased risk of severe retinopathy of prematurity in GA 24-26 and 27-29 weeks in the SGA group compared with the non-SGA group (adjusted OR = 1.68 and 1.59, respectively).In the analysis of long-term outcomes, the SGA group had a significantly increased risk of NDI throughout all GA subgroups (adjusted = 1.94, 1.33, and 1.35, respectively) in comparison with the non-SGA group. The SGA groups also had an increased risk of growth status <10th percentile at 2 years of age (p < 0.05). Conclusions: SGA VLBW premature infants had higher risks of neonatal death, growth status <10th percentile, and NDI at 2 years of corrected age compared with the non- SGA premature infants. Prenatal surveillance, postnatal attention, and long- term follow-up are warranted to improve the outcomes of VLBW SGA premature infants.

The effect of patient volume on mortality and morbidity of extremely low birth weight infants in Taiwan.

BACKGROUND: To assess whether the number of extremely low birth weight (ELBW) infants treated annually in neonatal intensive care units (NICUs) in Taiwan affects the mortality and morbidity of this patient population. METHODS: This retrospective cohort study included preterm infants with ELBW (≤1000 g). NICUs were divided into three subgroups according to the annual admissions of ELBW infants (low, ≤10; medium, 11-25; and high, >25). Perinatal characteristics, mortality, and short-term morbidities were compared between groups. RESULTS: A total of 1945 ELBW infants from 17 NICUs were analyzed (low-volume, n = 263; medium-volume, n = 420; and high-volume, n = 1262). After risk adjustments, infants from NICUs with low patient volumes were at a higher risk of death. The risk-adjusted odds ratios (aOR) for mortality were 0.61 (95% CI, 0.43-0.86) in the high-volume NICUs and 0.65 (95% CI, 0.43-0.98) in medium-volume NICUs, compared with infants admitted to low-volume NICUs. Infants in medium-volume NICUs had the lowest incidence of prenatal steroid exposure (58.1%, P < 0.001) and were associated with the highest risk of necrotizing enterocolitis (aOR, 2.35 [95% CI, 1.48-3.72]), severe intraventricular hemorrhage (aOR, 1.55 [95% CI, 1.01-2.28]), and bronchopulmonary dysplasia (aOR, 1.61 [95% CI, 1.10-2.35]). However, survival without major morbidity did not differ between the groups. CONCLUSION: The mortality risk was higher among ELBW infants admitted to NICUs with a low annual patient volume. This may emphasize the importance of systematically referring patients from these vulnerable populations to appropriate care settings.

Risk Factors of Language Delay at Two Years of Corrected Age among Very-Low-Birth-Weight Preterm Infants: A Population-Based Study.

Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of corrected age in this vulnerable population. VLBW infants, who were assessed at two years of corrected age using the Bayley Scale of Infant Development, third edition, were included using a population-based cohort database. Language delay was defined as mild to moderate if the composite score was between 70 and 85 and severe if the score was < 70. Multivariable logistic regression analysis was used to identify the perinatal risk factors associated with language delay. The study comprised 3797 VLBW preterm infants; 678 (18%) had a mild to moderate delay and 235 (6%) had a severe delay. After adjusting for confounding factors, low maternal education level, low maternal socioeconomic status, extremely low birth weight, male sex, and severe intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (PVL) were found to be significantly associated with both mild to moderate and severe delays. Resuscitation at delivery, necrotizing enterocolitis, and patent ductus arteriosus requiring ligation showed significant associations with severe delay. The strongest factors predicting both mild to moderate and severe language delays were the male sex and severe IVH and/or cystic PVL; thus, early targeted intervention is warranted in these populations.

Reduced Lung Function at Preschool Age in Survivors of Very Low Birth Weight Preterm Infants.

Background: Survivors of preterm birth are at risk of long-term respiratory consequences. The objective of this prospective study was to assess pulmonary function at preschool age of former very low birth weight (VLBW) preterm children. Methods: Lung function of children born preterm and term controls aged 5-6 years were assessed by spirometry. The results were converted to z-scores. A questionnaire regarding respiratory symptoms was completed. Associations to gestational age (GA), birth weight (BW), bronchopulmonary dysplasia (BPD), and perinatal factors were assessed. Results: In total, 85 VLBW preterm children and 29 term controls were studied. Of the preterm children, the mean GA was 28.6 ± 2.6 weeks and the mean BW was 1,047 ± 273 gm. Preterm children had significantly lower z-scores of forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and forced expiratory flow rate between 25-75% of FVC (FEF25-75), compared with term controls (-0.73 vs. 0.04, p = 0.002; -0.22 vs. 0.39, p = 0.003; -0.93 vs. 0.0, p < 0.001; respectively). Further segregation of the preterm group revealed significantly impaired FEV1, FEF25-75 in children at earlier gestation (≤ 28 weeks, n = 45), lighter at birth (≤ 1,000 g, n = 38), or with BPD (n = 55) compared with term controls (p < 0.05). There were significant negative relationships between the severity of BPD with FEV1, FVC, and FEF25-75 (p < 0.05). However, no correlation between lung function measurements and respiratory symptoms was found. Conclusions: VLBW preterm infants have reduced lung function at preschool age, especially among those with younger GA, lower BW, and BPD. Additional long-term follow-up of respiratory outcomes are needed for this vulnerable population.

Value of prenatal diagnosis of meconium peritonitis: Comparison of outcomes of prenatal and postnatal diagnosis.

Advancements in diagnostic modalities have improved the diagnosis of meconium peritonitis (MP) both in utero and ex utero. This study aimed to determine the efficacy of prompt prenatal and postnatal diagnoses of MP on the postnatal outcomes of these patients.We conducted a retrospective chart review of neonates with MP admitted to the Mackay Memorial Hospital Systems from 2005 to 2016. The prenatal diagnoses, postnatal presentations, surgical indications, operative methods, types of MP, operative findings, associated anomalies, morbidities, patient outcomes, and survival rates were analyzed. Morbidities included postoperative adhesion ileus, bacteremia, and short bowel syndrome. We also performed subgroup analyses of the morbidity and survival rates of prenatally versus postnatally diagnosed patients, as well as inborn versus outborn neonates.Thirty-seven neonates with MP were enrolled. Of this number, 24 (64.9%) were diagnosed prenatally. Twenty-two (59.5%) were born preterm. The most common prenatal sonographic findings included fetal ascites followed by dilated bowel loops. Abdominal distention was the most frequent postnatal symptom. Thirty-four (91.9%) neonates underwent surgery, whereas 3 were managed conservatively. Volvulus of the gastrointestinal tract was the most frequent anatomic anomaly. The total morbidity and survival rates were 37.8% and 91.9%, respectively. The morbidity and survival rates did not differ significantly between prenatally and postnatally diagnosed patients (37.5% vs 33.3%, P = 1.00; 91.7% vs 92.3%, P = 1.00, respectively). Inborn and outborn patients did not differ in terms of morbidity and survival rates (27.3% vs 53.3%, P = .17; 100% vs 80.0%, P = .06, respectively).Although not statistically significant, inborn MP neonates had higher survival rates when compared with outborn MP neonates. Prompt postnatal management at tertiary centers seemed crucial.

Retrospective study of prognostic factors in pediatric invasive pneumococcal disease.

Streptococcus pneumoniae remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of S. pneumoniae from a normally sterile site (e.g., blood, cerebrospinal fluid, synovial fluid, pericardial fluid, pleural fluid, or peritoneal fluid). The aim of this study is to survey the clinical manifestations and laboratory results of IPD and identify the prognostic factors of mortality. From January 2001 to December 2006, a retrospective review of chart was performed in a teaching hospital in Taipei. The hospitalized pediatric patients with the diagnosis of pneumonia, arthritis, infectious endocarditis, meningitis or sepsis were recruited. Among them, 50 patients were pneumococcal infections proved by positive culture results or antigen tests. Clinical manifestations, laboratory data and hospitalization courses were analyzed. The median age was 3.5-year-old and there were 30 male patients (60%). Eight patients (16%) had underlying disease such as leukemia or congenital heart disease. Hemolytic uremic syndrome (HUS) was observed in ten patients and extracorporeal membrane oxygenation (ECMO) was performed in three patients. Leukocytosis, elevated C-reactive protein and AST level were noted in most of the patients. The overall mortality rate was 10%. We found that leukopenia, thrombocytopenia and high CRP level were significant predictors for mortality. In conclusion, S. pneumoniae remains an important health threat worldwide and IPD is life-threatening with high mortality rate. We found leukopenia, thrombocytopenia, and high CRP levels to be associated with mortality in pediatric IPD, and these factors are worthy of special attention at admission. Although we failed to identify a statistically significant prognostic factor in multivariate analysis due to relatively small sample size, we suggest an aggressive antibiotic treatment in patients with these factors at admission. Further large-scale studies are warranted.

Risk factor analysis and molecular epidemiology of respiratory adenovirus infections among children in northern Taiwan, 2009-2013.

BACKGROUND/PURPOSE: Respiratory infections caused by human adenoviruses (HAdV) are worldwide, and have significantly increased recently in Taiwan. This study aimed to clarify the molecular epidemiology and risk factors of HAdV severe infections and pneumonia among Taiwanese children. METHODS: Patients with HAdV infections and hospitalized in a medical center between 2009 and 2013 were divided into severe or nonsevere HAdV infections based on whether or not they received intensive care. HAdV pneumonia was identified for comparison. The HAdV genotype was determined by sequencing the partial hexon and fiber genes. The nucleotide sequences were compared by phylogenetic analysis. RESULTS: The 176 patients (97 boys, 79 girls) had a median age of 3.7 years. The HAdV infections circulated year-round. HAdV B3 (54.5%) was the most common genotype, followed by HAdV C2 (21%), HAdV E4 (8%), and HAdV B7 (6.8%). Thirty-two patients needed intensive care. In multivariate analysis, the risk factors for severe HAdV infections were underlying neurologic diseases [odds ratio (OR): 164.9; p < 0.001], prematurity (OR: 10.9; p = 0.042), and HAdV B7 (OR: 39.5; p = 0.011). Twenty-nine patients had HAdV pneumonia. Patients with underlying neurologic diseases (OR 76.8; p < 0.001), airway anomaly (OR 15.1; p = 0.033), chronic lung diseases (OR 12.5; p = 0.047), weight < 3rd percentile (OR 5.5; p = 0.027), and HAdV B7 (OR 4.2; p = 0.002) had higher incidences of pneumonia. Four with underlying neurologic diseases died of acute respiratory distress syndrome. CONCLUSION: HAdV infections circulate all year-round. HAdV B7 is strongly related to severe infections and pneumonia. Underlying neurologic diseases and prematurity are risk factors for severe HAdV infections.

Risk factors associated with death in patients with severe respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. This retrospective study describes the clinical characteristics of severe RSV infection and determines the risk factors for death. METHODS: Patients were identified through a review of all patients discharged with a diagnosis of RSV lower respiratory tract infection and admitted to hospital in the pediatric intensive care unit (PICU) of a tertiary medical center between July 1, 2001 and June 30, 2010. The medical and demographic variables were recorded and analyzed. RESULTS: The 186 RSV-positive patients admitted to the PICU had a median age of 5.3 months (interquartile range 2.3-12.4 months) and included 129 boys and 57 girls. Among them, 134 had at least one underlying disease: prematurity in 92, neurological disease in 57, bronchopulmonary dysplasia in 40, congenital heart disease in 26, hematological malignancies in 11, and Down's syndrome in nine patients. The 10 patients who died from RSV-related causes had a median age of 20.8 months (interquartile range 6.6-89.2 months) and all had a comorbidity. In multivariate analysis, the risk factors for death in severe RSV infection were Down's syndrome (odds ratio 7.20, 95% confidence interval 1.13-45.76; p = 0.036) and nosocomial RSV infection (odds ratio 4.46, 95% confidence interval 1.09-18.27; p = 0.038). CONCLUSION: Down's syndrome and nosocomial RSV infection are significantly associated with death in severe RSV infections. Clinicians should be alert to these conditions.

Prolonged seasonality of respiratory syncytial virus infection among preterm infants in a subtropical climate.

OBJECTIVE: There is limited epidemiological data on the seasonality of respiratory syncytial virus (RSV) infection in subtropical climates, such as in Taiwan. This study aimed to assess RSV seasonality among children ≤24 months of age in Taiwan. We also assessed factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with RSV-associated hospitalization in preterm infants to confirm the appropriateness of the novel Taiwanese RSV prophylactic policy. STUDY DESIGN: From January 2000 to August 2010, 3572 children aged ≤24-months were admitted to Taipei Mackay Memorial Hospital due to RSV infection. The monthly RSV-associated hospitalization rate among children aged ≤24 months was retrospectively reviewed. Among these children, 378 were born preterm. The associations between GA, CA, and BPD and the incidence of RSV-associated hospitalization in the preterm infants were assessed. RESULTS: In children aged ≤24 months, the monthly distribution of RSV-associated hospitalization rates revealed a prolonged RSV season with a duration of 10 months. Infants with GAs ≤32 weeks and those who had BPD had the highest rates of RSV hospitalization (P<0.001). Preterm infants were most vulnerable to RSV infection within CA 9 months. CONCLUSIONS: Given that Taiwan has a prolonged (10-month) RSV season, the American Academy of Pediatrics' recommendations for RSV prophylaxis are not directly applicable. The current Taiwanese guidelines for RSV prophylaxis, which specify palivizumab injection (a total six doses until CA 8-9 months) for preterm infants (those born before 28(6/7) weeks GA or before 35(6/7) weeks GA with BPD), are appropriate. This prophylaxis strategy may be applicable to other countries/regions with subtropical climates.

Clinical experience of extracorporeal membrane oxygenation for acute respiratory distress syndrome associated with pneumonia in children.

BACKGROUND/PURPOSE: To describe a single center's experience with pediatric patients receiving extracorporeal membrane oxygenation (ECMO) for respiratory failure due to acute respiratory distress syndrome (ARDS) associated with pneumonia and to investigate the factors associated with mortality. METHODS: Retrospective chart review of all pediatric patients receiving ECMO for severe ARDS associated with pneumonia and sepsis from December 2001 to October 2009 in the pediatric intensive care unit (ICU) and cardiovascular surgery ICU at a tertiary medical center, to investigate the factors associated with mortality. RESULTS: Twelve patients had pneumonia and sepsis with progression to ARDS. The duration of intubation prior to ECMO was 19.92±10.40 hours. The duration of ECMO support was 241.08±194.93 hours. The range of PaO(2)/FiO(2) was 42-69.9, alveolar-arterial oxygen gradient (AaDO(2)) 602-645, and oxygenation index (OI) 27.4-68. The pre-ECMO intubation duration in the initial venoarterial ECMO group was significantly different from the venovenous ECMO group (9.4±10.93 vs. 151.25±152.16 hours). The overall survival to lung recovery rate was 66.7% (8/12) and survival to discharge rate 58.3%. The survival rate to lung recovery improved from 20% (between 2001 and 2003) to 100% (after 2004). Between the survival and nonsurvival groups, only ICU days and total intubated days were significantly longer in survivors. Although without statistical significance, the nonsurvivors tended to have lower white blood cell counts, higher C-reactive protein (CRP), and longer pre-ECMO intubation time. Seven of the 12 patients had bacterial pneumonia, higher CRP and creatinine values, and a lower hospital survival rate compared to the nonbacterial group (42.8% vs. 80%). CONCLUSION: Application of ECMO in pediatric patients with severe ARDS seems effective in improving survival, even under the conditions of pneumonia with septic shock.

Mondini dysplasia presenting as otorrhea without meningitis.

Mondini dysplasia is a rare inner ear malformation that is usually only diagnosed after recurrent meningitis. Surgical intervention is mandatory. This report highlights the case of a patient with Mondini dysplasia who presented with hearing impairment and otorrhea and was diagnosed and treated before the occurrence of meningitis, thus preventing morbidity and neurologic sequelae. Hearing impairment may be the only manifestation of Mondini dysplasia, and the benefit of hearing screening is emphasized. Temporal bone computed tomography should be considered in children with unilateral sensorineural or mixed-type hearing impairment.

Sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus syndrome.

SCALP syndrome is an acronym describing the coincidence of sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus). We present a fourth case of this syndrome.

The changing face of early-onset neonatal sepsis after the implementation of a maternal group B Streptococcus screening and intrapartum prophylaxis policy--a study in one medical center.

BACKGROUND: Early-onset sepsis (EOS) is the major cause of neonatal morbidity and mortality. Maternal group B Streptococcus (GBS) screening and intrapartum antibiotic prophylaxis (IAP) were implemented in our hospital in 2004. Our aim was to evaluate the effectiveness of the program and changes in pathogens and antibiotic susceptibility. METHODS: The medical charts of mothers and infants with EOS between January 2001 and November 2008 were retrospectively reviewed. EOS was defined as sepsis occurring within 72 hours of birth. Data were pooled and compared for January 2001 through September 2004 (Period 1, without GBS screening) and October 2004 through November 2008 (Period 2, with GBS screening and IAP). RESULTS: The GBS screening rate increased from 10.11% in 2004 to 65% in 2008 and the IAP rate increased from 40% in 2004 to 90% in 2008. The most common EOS pathogen in Period 1 was GBS (45.4%), which decreased to 20% in Period 2 (p=0.081; trend p=0.009). The percentage of EOS because of Escherichia coli in Period 1 was 40.9% but increased to 70% in Period 2 (p=0.059). E coli EOS increased in extremely low birth weight premature babies weighing 500-1000g from Period 1 to Period 2 (p=0.031). The incidence of ampicillin-resistant E coli EOS was relatively high, but no significant change (88.9% vs. 92.9%) after implementation of GBS screening and IAP was noted. CONCLUSION: GBS screening plus IAP is effective in decreasing the incidence of GBS EOS; however, an increase in EOS caused by E coli was noted. Monitoring of pathogens causing EOS is important for effective treatment.