Therapeutic strategy of patent ductus arteriosus in extremely preterm infants.

The ductus arteriosus is likely to close without treatment in most infants born at gestational age (GA) > 28 weeks (73%), and those with birth weight > 1000 g (94%). However, the rates of spontaneous ductal closure among less mature or smaller infants with respiratory distress syndrome are not known. Extremely preterm infants born at GA < 28 weeks are associated with a high risk of severe intraventricular hemorrhage (IVH) or pulmonary hemorrhage, which usually occur within 72 h after birth and affect mortality and long-term neurological development. These serious hemorrhagic complications may be closely related to hemodynamic changes caused by a hemodynamically significant patent ductus arteriosus (hs-PDA). While prophylactic indomethacin has been shown to reduce the rates of PDA, PDA ligation, severe IVH and early pulmonary hemorrhage, the available evidence does not support its prophylactic use in preterm infants. Symptomatic or late treatment is associated with lower success rate, and increased complications of a hs-PDA. The issue of "to treat or not to treat a PDA" is controversial. Considering the relationship between the effectiveness and timing of pharmacological treatment, early targeted treatment may be an alternative approach for the early identification of a hs-PDA in specific high-risk patient population, especially infants <26 weeks GA who are at the highest risk of severe IVH or pulmonary hemorrhage. Serial echocardiographic studies can be used to select patients who are candidates for early targeted medical treatment of hs-PDA. Surgical ligation of PDA, and transcatheter closure if proven to be safe, can be used as back-up therapy for patients who fail medical treatment and continue to have cardiopulmonary compromise.

Association of preterm birth and small for gestational age with metabolic outcomes in children and adolescents: A population-based cohort study from Taiwan.

BACKGROUND: Previous studies have identified preterm birth and/or small for gestational age (SGA) as risk factors for features of the metabolic syndrome, including high blood pressure, insulin sensitivity and atherosclerosis, occurring later in life, with controversial results. We conducted this population-based cohort study to investigate metabolic outcomes in those with former preterm birth and/or SGA status in Taiwan. METHODS: Data were obtained from Taiwan's universal National Health Insurance Research Database. From 1996 to 2004, 37,119 preterm infants, 3386 SGA infants, and 162,020 matched controls were included. We investigated the risk of the metabolic disease, including hypertension, diabetes, and hyperlipidemia, which had been recorded by the end of 2008. RESULTS: The preterm and SGA cohort, combined into one, had a significantly increased risk of developing metabolic disorders when compared with the comparison cohort (HR = 2.46, 95% CI = 2.02-3.01). We observed that children with former preterm and SGA status in Taiwan had a higher risk of developing hypertension (HR = 3.24, 95% CI = 1.58-6.67), Type 1 diabetes mellitus (HR = 1.80, 95% CI = 1.05-3.07), Type 2 diabetes mellitus (HR = 2.49, 95% CI = 1.98-3.14), and hyperlipidemia (HR = 2.14, 95% CI = 1.29-3.52). CONCLUSION: Our study revealed the risk of metabolic disease in those with preterm birth and/or SGA. Further studies with a longer duration of follow-up are required to confirm if there is a tendency for the metabolic syndrome to develop in this study cohort.

Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis.

Chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neurodevelopmental sequelae. Chorioamnionitis has been marked to a heterogeneous setting of conditions characterized by infection or inflammation or both, followed by a great variety in clinical practice for mothers and their newborns. Recently, a descriptive term: "intrauterine inflammation or infection or both" abbreviated as "Triple I" has been proposed by a National Institute of Child Health and Human Development expert panel to replace the term chorioamnionitis. It is particularly important to recognize that an isolated maternal fever does not automatically equate to chorioamnionitis. This article will review the current literature on chorioamnionitis, and introduce the concept of Triple I, as well as recommendations for assessment and management of pregnant women and their newborns with a diagnosis of Triple I.

Efficacy of Medical Treatment for Infantile Hypertrophic Pyloric Stenosis: A Meta-analysis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is a common disease in infancy. Pyloromyotomy is universally considered the treatment for IHPS; however, oral or intravenous atropine has been reappraised for the treatment of IHPS in the past 20 years. We investigated the efficacy of atropine in the medical management of IHPS by using meta-analysis and investigated the sonographic changes of the pyloric canal, as well as the efficacy and adverse effects of atropine. METHODS: Information was retrieved from PubMed, Ovid, and MEDLINE. The efficacy and adverse effects of atropine treatment for IHPS were reviewed using the standard process of meta-analysis. RESULTS: Eleven articles were obtained. Five reports showed that 77 of 110 (70%) infants who were administered oral atropine benefitted by the induced remission of IHPS. Six reports showed that 288 of 345 (83.5%) patients who were treated initially with intravenous atropine then changed to oral atropine showed beneficial effects and had no serious side effects. Time to pyloric muscle normalization ranged from 5 weeks to 15 months. CONCLUSION: The study results indicate that atropine is a possible alternative treatment for IHPS, particularly in infants with major concurrent disease, and is safe without obvious side effects.

Circulatory Management Focusing on Preventing Intraventricular Hemorrhage and Pulmonary Hemorrhage in Preterm Infants.

The goal of modern neonatal care of extremely preterm infants is to reduce mortality and long-term neurological impairments. Preterm infants frequently experience cerebral intraventricular or pulmonary hemorrhage, which usually occurs within 72 hours after birth and can lead to long-term neurological sequelae and mortality. These serious hemorrhagic complications are closely related to perinatal hemodynamic changes, including an increase in the afterload on the left ventricle of the heart after the infant is separated from the placenta, and an increased preload from a left-to-right shunt caused by a hemodynamically significant patent ductus arteriosus (PDA). The left ventricle of a preterm myocardium has limited ability to respond to such an increase in afterload and preload, and this can result in cardiac dysfunction and hemodynamic deterioration. We suggest that delayed umbilical cord clamping or umbilical cord milking to maintain optimal blood pressure and systemic blood flow (SBF), careful assessment to keep the afterload at an acceptable level, and a strategy of early targeted treatment of significant PDA to improve perfusion during this critical time period may reduce or prevent these serious complications in preterm infants.

Clonal dissemination of invasive and colonizing clonal complex 1 of serotype VI group B Streptococcus in central Taiwan.

BACKGROUND/PURPOSE: The aim of this study was to investigate clinical presentation, serotype distribution and genetic correlation of group B streptococcus (GBS) diseases. Since serotype VI prevalence far exceeded that reported in prior studies, genetic relationship of isolates was further analyzed. METHODS: GBS isolates obtaining from patients with invasive diseases and pregnant women with colonization between June 2007 and December 2010 were analyzed. All isolates were tested for serotypes by multiplex PCR assay and pulsed-field gel electrophoresis (PFGE). Serotype VI isolates were further analyzed by multilocus sequence typing (MLST). RESULTS: A total of 134 GBS isolates were recovered from blood of 126 patients with invasive disease (94.0%) and anogenital swabs of 8 pregnant women (6.0%). Most common serotype was Ib (21.6%), followed by V (20.1%), VI (18.7%), III (15.7%), II (11.9 %), Ia (11.2%), and IX (0.7%). Serotype VI was also the leading type in infants with early onset disease (EOD; 3/8, 37.5%) and colonizing pregnant women (3/8, 37.5%). PFGE distinguished 33 pulsotypes, reflecting genetic diversity among GBS isolates. Among 25 serotype VI isolates tested, 14 were ST-1, seven were ST-679, three were ST-678, one was ST-681, and distributed into four PFGE pulsotypes. ST-678, ST-679, and ST-681 were novel sequence types; ST-678 and ST-679 are single-locus variants of ST-1 that belongs to clonal complex (CC) 1. CONCLUSION: CC1 dissemination of serotype VI GBS thus emerges as an important invasive pathogen in infants and nonpregnant adults in central Taiwan. Serotype prevalence of GBS must be continuously monitored geographically to guide prevention strategy of GBS vaccines.

Multidrug-resistant Acinetobacter baumannii infection among neonates in a neonatal intensive care unit at a medical center in central Taiwan.

BACKGROUND: Few studies have focused on multidrug-resistant Acinetobacter baumannii (MDRAB) infection in neonates. The aim of this study was to investigate risk factors for mortality in neonates with MDRAB infection. METHODS: This retrospective case-series study was conducted at the Children's Hospital of China Medical University, Taichung, Taiwan. All patients hospitalized between January 2010 and December 2013 in the neonatal intensive care unit (NICU) with MDRAB infections were reviewed. RESULTS: A total of 67 isolates from 59 neonatal patients were positive for MDRAB. Of the 67 isolates, 38 were from blood (56.72%), 16 from sputum (23.88%), seven from pus (10.45%), three from ascites (4.48%), two from cerebrospinal fluid (2.99%), and one from pleural fluid (1.49%). There were five episodes of MDRAB clusters consisting of 28 cases during the study period. The mortality rate due to MDRAB sepsis was 20.34% (12/59). The statistically significant risk factors for mortality due to MDRAB infection were being infected with MDRAB within 7 days of admission to the NICU, use of umbilical vein catheters, absolute neutrophil count < 1500/mm(3), platelet count < 100,000/mm(3), and a delay in initiating adequate antibiotic treatment. CONCLUSION: MDRAB infection is responsible for a high mortality rate among neonates in the NICU, especially in those who have neutropenia or thrombocytopenia. Infection control and appropriateness of the initial antimicrobial agent with colistin play an important role in reducing mortality.

Neonatal outcomes of extremely preterm infants from taiwan: comparison with Canada, Japan, and the USA.

BACKGROUND: This study compared the current trend in survival rates and morbidity for very low birth weight (VLBW) infants in five Medical Training Centers of Prematurity for the Premature Baby Foundation of Taiwan (PBFT), with the outcomes from the USA, National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN), the Canadian Neonatal Network (CNN), and the Neonatal Research Network of Japan (NRNJ). METHODS: The survival rates of VLBW infants according to gestational age (GA) and major morbidities were compared between networks (Taiwan, USA, Canada, and Japan). Taiwanese data for VLBW infants of GA ≤28 weeks between 2007 and 2012 were obtained from the "PBFT Annual Conferences of Premature Care" reports defining survival rate as neonates that survived to the time of discharge. Major morbidities included severe neurological injury (Grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia), bronchopulmonary dysplasia, severe retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, and patent ductus arteriosus. RESULTS: The survival rates of VLBW infants of GA ≤28 weeks from the PBFT (Taiwan), NICHD NRN (USA), CNN (Canada), and NRNJ (Japan) were 77% (1323/1718), 72% (6859/9575), 82% (2353/2872), and 89% (4489/5069), respectively. The annual survival rates in Taiwan from 2007 to 2012 were 72%, 76%, 76%, 74%, 77%, and 78%, respectively. When GA from ≤23 weeks to 28 weeks was assessed in Taiwan, the survival rates of VLBW infants according to each week were 22%, 50%, 70%, 80%, 88%, and 92%, respectively. The survival rate, especially at lower GAs, was highest in the NRNJ (Japan). The major difference between Taiwan and Japan was attributed to the lower survival rates at lower GA (≤26 weeks) in Taiwan. Japan had the lowest rates of major morbidities among the four countries. CONCLUSION: The survival rate of VLBW infants has improved over the past 6 years in Taiwan. It is higher than the USA, but lower than Canada and Japan. However, the results from Taiwan are from five Medical Training Centers for the PBFT rather than from a population-based study. It is crucial to have a nationwide neonatal research network to develop new practical approaches for VLBW infants in Taiwan.

Optimizing nutrition in preterm infants.

Extrauterine growth restriction is common in very preterm infants. The incidence in very-low-birth-weight infants ranges between 43% and 97% in various centers, with a wide variability due to the use of different reference growth charts and nonstandard nutritional strategies. Extrauterine growth restriction is associated with an increased risk of poor neurodevelopmental outcome. Inadequate postnatal nutrition is an important factor contributing to growth failure, as most very preterm infants experience major protein and energy deficits during neonatal intensive care unit hospitalization. First-week protein and energy intake are associated with 18-month developmental outcomes in very preterm infants. Early aggressive nutrition, including parenteral and enteral, is well tolerated in the very preterm infant and is effective in improving growth. Continued provision of appropriate nutrition (fortified human milk or premature formula) is important throughout the growing care during the hospitalization. After discharge, exclusively breast-fed infants require additional supplementation. If formula-fed, nutrient-enriched postdischarge formula should be continued for approximately 9 months corrected age. Supplementation of the preterm formulas with protein would increase the protein/energy ratio (3 g/100 kcal), leading to increased lean mass with relatively decreased fat deposition. Further research is required to optimize the nutritional needs of preterm infants and to evaluate the effects of nutritional interventions on long-term growth, neurodevelopment, and other health outcomes.

Efficacy of creamatocrit technique in evaluation of premature infants fed with breast milk.

BACKGROUND: Most premature babies are discharged with low body weight. Creamatocrit represents the lipid concentration of breast milk. We expected the creamatocrit technique could be applied in the nutrition plan for premature infants who were exclusively fed by human milk. METHODS: Breast milk samples were obtained from the mothers whose babies were admitted to the neonatal intensive care unit or sick baby room. The breast milk provider was enrolled under the criteria of stable breast milk expression 2 weeks after having given birth. Breast milk was collected for 7 consequent days. Creamatocrit technique and calorie analysis were performed on the processed breast milk samples. RESULTS: Fourteen pairs of mothers and infants were enrolled in our study. The median gestational age and birth weight were 29 weeks (27-36 weeks) and 1,393 g (680-3050 g), respectively. The mean calorie and creamatocrit values for all the 98 breast milk samples were 0.67 kcal/mL and 5.98%, respectively. The linear correlation between creamatocrit value and laboratory-measured calories was found to be calories (kcal/mL)=0.39+0.048×creamatocrit (%) (p<0.05). CONCLUSION: We established the relation equation of creamatocrit and calories for the first time in Chinese population, which is convenient and accurate for evaluating calories provided for premature infants fed with breast milk.

Neonatal intracranial aneurysm rupture treated by endovascular management: a case report.

Pediatric intracranial aneurysm rupture is rare, and is traditionally managed by surgical clipping. To the best of our knowledge, endovascular embolization of aneurysms in neonates has not previously been reported in Taiwan. We report a 9-day-old boy with intracranial aneurysms who underwent endovascular embolization, representing the youngest reported case in Taiwan. The 9-day-old boy presented with non-specific symptoms of irritable crying, seizure and respiratory distress. Computed tomography disclosed intraventricular hemorrhage, subarachnoid hemorrhage and focal intracranial hemorrhage around the right cerebellum. Subsequent computed tomographic angiography showed two sequential fusiform aneurysms, measuring 3 mm, located in the right side posterior inferior cerebellar artery (PICA). The patient underwent endovascular embolization because of the high risk of aneurysm re-rupture and the impossibility of surgical clipping due to the fusiform nature of the aneurysms. A postembolization angiogram revealed complete obliteration of the right distal PICA and proximal aneurysm. The distal PICA aneurysm was revascularized from the collateral circulation, but demonstrated a slow and delayed filling pattern. The patient's condition remained stable over the following week, and he was discharged without anticonvulsant therapy. No significant developmental delay was noted at follow-up at when he was 3 months old. This case emphasizes the need for clinical practitioners to consider a diagnosis of intracranial hemorrhage in neonates with seizure and increased intracranial pressure. Neonatal intracranial aneurysms can be treated safely by endovascular treatment.

Discriminating "top-heavy" versus "bottom-heavy" geometric patterns in 2- to 4.5-month-old infants.

Simion, Valenza, Macchi Cassia, Turati, and Umiltà (2002) suggested that newborns preferred "top-heavy" stimuli and such bias may account for neonatal face preference. However, convergent evidence for the discriminability between the top-heavy versus bottom-heavy patterns has not been demonstrated. We used a modified familiarization/novelty procedure (Chien, Palmer, & Teller, 2003) to assess basic discriminability between "top-heavy" and "bottom-heavy" geometric patterns in 2- to 4.5-month-old infants. Each infant was tested with three types of top-heavy and bottom-heavy geometric figures and received both familiarized-to-top-heavy and familiarized-to-bottom-heavy conditions. If infants of this age can discriminate the two configurations and there is no intrinsic bias toward either pattern, we expected to see significant and about equal novelty effects in both familiarization conditions. If there is a strong intrinsic bias for the top-heavy configuration, we expect to see a greater preference for the top-heavy patterns in the familiarization-to-bottom-heavy condition. Our results (N=24) showed significant and equal novelty preferences in both familiarization conditions across age and figure types, suggesting a reliable discriminability between top-heavy and bottom-heavy configurations and there is no intrinsic bias towards either configuration at this age.

Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants.

OBJECTIVE: To evaluate growth and neurodevelopmental outcomes in preterm very low birth weight (PVLBW) infants treated with oral probiotics for the prevention of necrotizing enterocolitis (NEC). STUDY DESIGN: A prospective follow-up study was performed in a cohort of PVLBW infants enrolled in a single center with a masked randomized control trial to evaluate the efficacy of oral probiotics in preventing NEC. Growth measures included weight, length, and head circumference. Neurologic and sensory performance was evaluated with standard techniques. Psychometric parameters were measured used the Bayley Scales of Infant Development II (BSID-II). The studies were performed at 3 years corrected age. The primary outcome was death or neurodevelopmental impairment. RESULTS: Of the 367 subjects enrolled in trial, 301 (89.9%) were evaluated (153 in the probiotics group and 148 in the control group). There were no significant differences in growth or in any of the neurodevelopmental and sensory outcomes between the 2 groups. CONCLUSIONS: Oral probiotics given to PVLBW infants at 1 week after birth to reduce the incidence of NEC did not affect growth and neurodevelopmental and sensory outcomes at 3 years corrected age.