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Showing papers in "Pediatrics and Neonatology in 2017"


Journal ArticleDOI
TL;DR: MDRs are the most common cause of sepsis at the NICU and are associated with higher mortality compared with non-MDROs and more delay in providing targeted antimicrobial therapy, according to clinical and laboratory data.
Abstract: Background Sepsis in the neonatal intensive care unit (NICU) remains one of the most significant causes of morbidity and mortality, especially for preterm newborns. Multi-drug resistant organisms (MDROs) are emerging as important pathogens that cause neonatal sepsis in NICU. Therefore, studying the epidemiology, clinical features, and outcome caused by MDROs vs. non-MDROs, and identifying risk factors that may predispose patients to sepsis by MDROs are important. Methods Episodes of blood culture-proven sepsis (age: 0–90 days) in the NICU at our institution from January 2012 to December 2015 were retrospectively reviewed. Collected data included demographics, signs at time of sepsis, laboratory values, microbiologic results, and final outcome. We compared clinical and laboratory data and final outcome for patients with sepsis due to MDROs vs. non-MDROs. Multivariate analysis was performed on variables with a P value of Results Sixty-eight episodes of sepsis (ages 0–54 days, median 7 days; 34 female; 81% premature) were caused by Gram-negative bacteria ( n = 42; 62%), Gram-positive bacteria ( n = 21; 31%), or Candida ( n = 5; 7%). The most common organisms that were isolated were Acinetobacter baumannii (27%), Klebsiella pneumoniae (22%), coagulase-negative staphylococcus (CoNS) (18%), group B streptococcus (10%), and E scherichia coli (6%). Compared with non-MDROs ( n = 16; 31%, excluding CoNS and Candida ), MDROs ( n = 35; 69%) were associated with higher mortality ( P = 0.002) and more delay in providing targeted antimicrobial therapy ( P = 0.002) (based on antimicrobial susceptibility tests). Sepsis due to the most resistant organisms ( A. baumannii and K. pneumoniae Carbapenemase [KPC]-producing bacteria, n = 20; 39%) was associated with higher mortality ( P = 0.001) and significantly associated with exposure to carbapenem and vancomycin before onset of sepsis (cases exposed = 13/20; 65%, P Conclusion MDROs are the most common cause of sepsis at our NICU and are associated with higher mortality compared with non-MDROs. Previous exposure to carbapenem and vancomycin was associated with sepsis caused by the most resistant organisms.

75 citations


Journal ArticleDOI
TL;DR: The current literature on chorioamnionitis is reviewed, the concept of Triple I is introduced, as well as recommendations for assessment and management of pregnant women and their newborns with a diagnosis of triple I are introduced.
Abstract: 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.

74 citations


Journal ArticleDOI
TL;DR: It is recommended to repeat the screening test in pre-term, LBW and very-low- birth-weight infants at age of two, six and ten weeks by measuring TSH and FT4 levels simultaneously and considering TSH = 10 mU/L as the cutoff level for positive and suspicious cases.
Abstract: Evidence from different screening programs indicated that the rate of congenital hypothyroidism (CH) was higher in pre-term and low-birth-weight (LBW) newborns than normal ones. Incomplete development of hypothalamic–pituitary axis in this group of neonates results in the delayed rise of TSH and missing cases with CH. Hence, there is a great need for a practicable systematic screening method for proper diagnosis of CH in this group of neonates. In this review, we systematically reviewed papers with the following key words ([Congenital Hypothyroidism AND Screening AND Thyroxine AND Thyroid Stimulating Hormone AND Low Birth Weight AND Premature]) in international electronic databases including PubMed, Scopus, and Google Scholar. After quality assessment of selected documents, data of finally included papers were extracted. In this review, 1452 papers (PubMed: 617; Scopus: 714; Google scholar: 121) were identified through electronic database search. One hundred and ninety four articles were assessed for eligibility, from which 36 qualified articles were selected for final evaluation. From the reviewed articles, 38.9%, 11.11% and 8.3% recommended rescreening in this group of neonates, lowering the screening cutoff of TSH and using cutoffs according to the gestational age, respectively. Some of them (13.9%) recommended using both TSH and T4 for screening of preterm infants. After reviewing available data, we recommend repeating the screening test in pre-term, LBW and very-low- birth-weight (VLBW) infants at age of two, six and ten weeks by measuring TSH and FT4 levels simultaneously and considering TSH = 10 mU/L as the cutoff level for positive and suspicious cases.

67 citations


Journal ArticleDOI
TL;DR: RBC transfusion has a negative impact on survival in ELBW infants and increases the risk of developing ROP and affects late neurodevelopment, and decisions of blood transfusion in these very immature infants should be made cautiously taking these deleterious results into consideration.
Abstract: Background Red blood cell (RBC) transfusion is often considered a life-saving measure in critically ill neonates. The smallest and least mature infants tend to receive the largest amount of transfusions. RBC transfusion itself has also been suggested as an independent risk factor of poor clinical outcome in critical patients. Our aim is to study if there are associations between RBC transfusion and in-hospital mortality, short-term morbidities, and late neurodevelopmental outcome in extremely low birth weight (ELBW) preterm infants. Methods A cohort of ELBW preterm infants admitted to our neonatal intensive care unit from January 2009 to December 2010 were recruited. The number of RBC transfusions within 7 days, 30 days, and 60 days of life were recorded. Clinical outcomes including in-hospital mortality, development of retinopathy of prematurity (ROP), necrotizing enterocolitis, chronic lung disease, and later neurodevelopmental outcome were assessed with follow-up of up to 2 years of age. Multivariable logistic regression was used to estimate the associations between RBC transfusion and clinical outcomes. Results A total of 98 ELBW preterm infants survived at the time of discharge. Of these survivors, the mean numbers of RBC transfusions were 2.5 ± 1.7, 7.4 ± 3.1, and 11.3 ± 4.5 times within 7 days, 30 days, and 60 days after birth, respectively. The number of transfusions within 7 days of life was correlated with risk of death before 1 month of age (odds ratio: 1.54, 95% confidence interval: 1.04–2.27, p = 0.03) and the number of transfusions within 30 days was correlated with risk of developing threshold ROP (odds ratio: 1.27, 95% confidence interval: 1.04–1.55, p = 0.02). The number of transfusions within 7 days of life was positively correlated with cognitive performance (Mental Developmental Index score) at 18–24 months of corrected age. Conclusion RBC transfusion has a negative impact on survival in ELBW infants. It increases the risk of developing ROP and affects late neurodevelopment. Decisions of blood transfusion in these very immature infants should be made cautiously taking these deleterious results into consideration.

64 citations


Journal ArticleDOI
TL;DR: Diuretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas beta-blockers and devices for electric therapy are less used in children than in adults.
Abstract: Pediatric heart failure represents an important cause of morbidity and mortality in childhood. Currently, there are well-established guidelines for the management of heart failure in the adult population, but an equivalent consensus in children is lacking. In the clinical setting, ensuring an accurate diagnosis and defining etiology is essential to optimal treatment. Diuretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas beta-blockers and devices for electric therapy are less used in children than in adults. In the end-stage disease, heart transplantation is the best choice of treatment, while a left ventricular assist device can be used as a bridge to transplantation (due to the difficulties in finding organ donors), recovery (in the case of myocarditis), or destination therapy (for patients with systemic disease).

63 citations


Journal ArticleDOI
TL;DR: Evidence is provided of the importance of both individual- and community-level factors in determining childhood undernutrition, as well as the various predictors discussed in this study, in order to reduce undernutrition in children and contribute to their well-being.
Abstract: Background Undernutrition is a major global public health problem among children under the age of 5 years. We aimed to untangle the effects of a wide range of individual- and community-level socioeconomic factors on the risks of childhood undernutrition in Malawi. Methods We analyzed 6384 women-infant pairs from the 2004 and 2010 Malawi Demographic and Health Surveys (MDHSs). The undernutrition status was assessed by three domains of stunted (height-for-age), wasted (weight-for-height), and underweight (weight-for-age). We constructed generalized estimating equation logistic models to analyze associations of individual- and community-level characteristics with childhood undernutrition. Results About 48.4% of the children were stunted, 4.5% were wasted, and 14.4% were underweight. At the individual level, the risk of childhood undernutrition was significantly higher in males, children with a small birth size, children with a diarrheal episode in the last 2 weeks, children that were a product of multiple births, children born to mothers with either a low socioeconomic status, or a poor education, or who were underweight, and children born in the year 2004. At community level, children born in communities with low and medium wealth, and in communities with low and medium female educational attainment were more likely to be undernourished. Unexpectedly, the maternal HIV status was not associated with childhood undernutrition at either the individual or community level. Conclusion This study provides evidence of the importance of both individual- and community-level factors in determining childhood undernutrition. Interventions against childhood undernutrition should consider the various predictors discussed in this study in order to reduce undernutrition in children and contribute to their well-being.

52 citations


Journal ArticleDOI
TL;DR: This review article summarizes the key points and recommendations regarding TH for newborns with HIE, including selection criteria for TH, choices of method and equipment, and outcomes.
Abstract: Therapeutic hypothermia (TH) is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE). The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1) selection criteria for TH; (2) choices of method and equipment for TH; (3) TH prior to and during transport; (4) methods for temperature maintenance, monitoring, and rewarming; (5) systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism; (6) monitoring and management of seizures; (7) neuroimaging, prognostic factors, and outcomes; and (8) adjuvant therapy for TH.

51 citations


Journal ArticleDOI
TL;DR: It is demonstrated in an ex-vivo model that hypoxic conditions initiated a destructive process of the epithelial barrier and the expression of the tight junction proteins ZO-1 and occludin were significantly down regulated in NEC specimens.
Abstract: Background & aims Necrotizing Enterocolitis (NEC) is a severe inflammatory disorder of the intestine endangering the health and survival of preterm infants. It is well established that the gut barrier is severely damaged in NEC patients, nonetheless an in depth investigation of modifications at the transcriptional and translational levels of tight junction genes and proteins during NEC are still missing. The aim of this study was to investigate changes in the expression of tight junctions and other associated proteins during NEC and determine their correlation to the disease severity. Methods We examined intestinal specimens from six NEC patients and compared them with six control specimens from patients that underwent surgeries for reasons other than NEC. The expression of genes was analyzed by real time PCR and protein expression by immunohistochemistry. Results The tight junction genes ZO-1, occludin, cingulin and claudin-4 were significantly down regulated in NEC. Furthermore TLR4, BAX and SIRT1 genes were found to be significantly down regulated while HIF-1A showed a trend of up regulation in NEC patients. These changes were found to correlate with the severity of the disease. Additionally we demonstrated in an ex-vivo model that hypoxic conditions initiated a destructive process of the epithelial barrier. We also showed that the expression of the tight junction proteins ZO-1 and occludin were significantly down regulated in NEC specimens. Conclusions The expression of tight junction proteins and their encoding genes are significantly altered in NEC. We surmise that SIRT1 and HIF-1A may play a role in controlling these effects.

49 citations


Journal ArticleDOI
TL;DR: Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death.
Abstract: Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death Among fetal primary cardiac tumors, rhabdomyomas are most common, followed by teratomas, fibromas, hemangiomas, and myxomas Everolimus, a mammalian target of rapamycin inhibitor, has been reported to be an effective drug to cause tumor remission in three neonates with multiple cardiac rhabdomyomas Neonatal cardiac surgery for the resection of primary cardiac tumors found by fetal echocardiography has been reported sporadically However, open fetal surgery for pericardial teratoma resection, which was performed successfully via a fetal median sternotomy in one case report, could be a promising intervention to rescue these patients with large pericardial effusions These recent achievements undoubtedly encourage further development in early management of fetal cardiac tumors Owing to the rarity of fetal primary cardiac tumors, relevant information in terms of prenatal diagnosis, treatment, and prognosis remains to be clarified

46 citations


Journal ArticleDOI
TL;DR: Intrahepatic cholestasis of pregnancy and meconium aspiration syndrome may be new risk factors for NEC in preterm infants.
Abstract: Background Necrotizing enterocolitis (NEC) in neonates is devastating, and risk-factor identification is crucial. This study aimed to evaluate risk factors for NEC in different gestational age (GA) groups. Methods Risk factors associated with NEC were investigated using a retrospective case-control design. Patients with Bell's Stage NEC ≥ II were divided into three groups based on GA: I, Results A total of 238 cases and 476 controls were enrolled. Variation in the months when NEC was diagnosed was noted, with a peak in January and a trough in August. Intrahepatic cholestasis of pregnancy and transfusion with packed red blood cells were significantly associated with NEC in preterm infants. Meconium aspiration syndrome was an independent risk factor for a greater chance of NEC development in full-term infants. Postnatal asphyxia and sepsis were associated with an increased risk of NEC in all groups. Probiotic use was associated with a reduced risk of NEC. Patients aged >34 weeks with congenital heart disease were more likely than controls to have NEC. Conclusion Intrahepatic cholestasis of pregnancy and meconium aspiration syndrome may be new risk factors for NEC.

44 citations


Journal ArticleDOI
TL;DR: A biventricular repair consisting of the reconstruction of a competent monocuspid tricuspid valve, right ventriculorrhaphy, subtotal atrial septal defect closure, and aggressive reduction atrioplasty is suitable for most patients, and 1.5-ventricular repair is indicated for patients with poor right ventricular function.
Abstract: Ebstein's anomaly is uncommon. Genetic bases of this congenital heart defect may be related to the mutations in myosin heavy chain 7 and NKX2.5, among others. Asymptomatic patients with Ebstein's anomaly can be conservatively treated and kept under close follow-up, whereas surgical operation is indicated for those patients with evidence of right heart dilation and progressively impaired ventricular systolic function. A biventricular repair consisting of the reconstruction of a competent monocuspid tricuspid valve, right ventriculorrhaphy, subtotal atrial septal defect closure, and aggressive reduction atrioplasty is suitable for most patients, and 1.5-ventricular repair (bidirectional Glenn shunt) is indicated for patients with poor right ventricular function; by contrast, heart transplantation is used in patients with severe left ventricular dysfunction.

Journal ArticleDOI
TL;DR: The basic pharmacology, current therapeutic uses, adverse effects, controversies as well as present and future research of caffeine are updated.
Abstract: Caffeine citrate is one of the most prescribed drug in the present day NICU for apnea. Its efficacy, tolerability, wide therapeutic index and safety margin has made it the drug of choice among the methylxanthines. Its therapeutic uses in apnea of prematurity, mechanical ventilation, bronchopulmonary dysplasia has made it a "silver bullet" in neonatology. However, there are still controversies surrounding this drug. This review is aimed to update the reader about the basic pharmacology, current therapeutic uses, adverse effects, controversies as well as present and future research of caffeine.

Journal ArticleDOI
TL;DR: OC application for VLBW infants is safe and practical in a neonatal intensive care unit setting and is associated with increased rates of breast milk feeding.
Abstract: Background Oropharyngeal colostrum (OC) application strategies have been shown to be feasible and safe for very low birth weight (VLBW) infants. Evidence to support the nutritional and clinical advantages of OC care remains somewhat theoretical. The objectives of this study were to a) confirm the feasibility and safety of OC application in preterm infants and b) determine if OC application is associated with improved nutritional and clinical outcomes from birth to discharge. We hypothesized that OC application in the first few days would promote sustained breast milk feedings through discharge. Methods An observational longitudinal study was conducted in 133 VLBW infants during 2013–14, after an OC protocol was adopted. Maternal and infant characteristics, infant vital signs during administration, nutritional outcomes, and common neonatal morbidities were assessed and compared to 85 age- and weight-matched VLBW infants from a retrospective control cohort from 2012, prior to the implementation of the OC protocol. Results There were no adverse events or changes in vital signs during the application of OC. VLBW infants who received OC continued to receive the majority of their enteral feeds from human breast milk at six 6 of age and through discharge ( p Conclusion OC application for VLBW infants is safe and practical in a neonatal intensive care unit setting and is associated with increased rates of breast milk feeding.

Journal ArticleDOI
TL;DR: The study revealed the risk of metabolic disease in those with preterm birth and/or SGA status in Taiwan, and found a significantly increased risk of developing metabolic disorders.
Abstract: 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.

Journal ArticleDOI
TL;DR: The mainstay therapy of PPHN includes treatment of underlying causes, maintenance of adequate systemic blood pressure, optimized ventilator support for lung recruitment and alveolar ventilation, and pharmacologic measures to increase pulmonary vasodilation and decrease pulmonary vascular resistance.
Abstract: Persistent pulmonary hypertension (PPHN) is a consequence of failed pulmonary vascular transition at birth and leads to pulmonary hypertension with shunting of deoxygenated blood across the ductus arteriosus (DA) and foramen ovale (FO) resulting in severe hypoxemia, and it may eventually lead to life-threatening circulatory failure. PPHN is a serious event affecting both term and preterm infants in the neonatal intensive care unit. It is often associated with diseases such as congenital diaphragmatic hernia, meconium aspiration, sepsis, congenital pneumonia, birth asphyxia and respiratory distress syndrome. The diagnosis of PPHN should include echocardiographic evidence of increased pulmonary pressure, with demonstrable right-to-left shunt across the DA or FO, and the absence of cyanotic heart diseases. The mainstay therapy of PPHN includes treatment of underlying causes, maintenance of adequate systemic blood pressure, optimized ventilator support for lung recruitment and alveolar ventilation, and pharmacologic measures to increase pulmonary vasodilation and decrease pulmonary vascular resistance. Inhaled nitric oxide has been proved to treat PPHN successfully with improved oxygenation in 60–70% of patients and to significantly reduce the need for extracorporeal membrane oxygenation (ECMO). About 14%–46% of the survivors develop long-term impairments such as hearing deficits, chronic lung disease, cerebral palsy and other neurodevelopmental disabilities.

Journal ArticleDOI
TL;DR: awareness of the associated risk factors and appropriate interventions may improve the outcome of necrotizing enterocolitis in different birth weight subgroup in Chinese neonatal units.
Abstract: Background We retrospectively investigated incidence, morbidity, and mortality of neonatal necrotizing enterocolitis in China, with special emphasis on determining the predictors of necrotizing enterocolitis associated mortality. Methods We identified neonates as having necrotizing enterocolitis if they met the accepted diagnostic criterion. Data pertaining to antenatal period, labor and birth, and the postnatal course of illness were collected. Multivariate analysis and logistic regression were used to analyze the risk factors. Results There were 1167 cases of necrotizing enterocolitis identified from the 95 participating NICUs in mainland China in 2011, with the incidence of 2.50% and 4.53% in LBW (birth weight P = 0.003) and stage 3 NEC (OR: 8.09, 95% CI 2.80–23.3, P P P Conclusions Necrotizing enterocolitis remains an important cause of morbidity and mortality in prematurely born neonates in Chinese neonatal units. Awareness of the associated risk factors and appropriate interventions may improve the outcome of necrotizing enterocolitis in different birth weight subgroup.

Journal ArticleDOI
TL;DR: This is the first study in the English literature providing evidence of the influence of platelet dysfunction on the spontaneous closure of ductus arteriosus in prematurity.
Abstract: Background This study aims at evaluating the influence of platelet count, platelet mass index, and platelet function on the spontaneous closure of ductus arteriosus in prematurity. Methods All preterm babies were divided into two groups, including Group 1 with “open PDA” and Group 2 with “closed PDA”. The variables of platelet count, mean platelet volume, platelet mass index, and platelet function were analyzed and compared between two groups of patients to identify the factors that significantly influenced spontaneous closure of ductus arteriosus. Results Twenty-four patients were in the “open PDA” group, whereas 36 patients were in the “closed PDA” group. Mean GA and BW were 27.6 ± 1.8 (23.1–30.4) and 28 ± 1.6 (23.4–30.6) weeks and 1009 ± 270 (585–1480) g and 1035 ± 298 (505–1500) g in “open PDA” and “closed PDA” groups, respectively (p > 0.05). The incidence of “Collagen-ADP > 130 s” was significantly higher in the “open PDA” group, and the levels of hemoglobin and hematocrit were significantly lower in the “open PDA” group (p 130 s (OR: 5.7 CI: 1.55–21.3) are two independent factors associated with ductal patency. Conclusion This is the first study in the English literature providing evidence of the influence of platelet dysfunction on the spontaneous closure of ductus arteriosus in prematurity. Longer collagen-ADP duration is identified as a risk factor of ductal closure.

Journal ArticleDOI
TL;DR: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers, and S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.
Abstract: Background Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. Methods The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). Results The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. Conclusion The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.

Journal ArticleDOI
TL;DR: Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates, and high-quality and adequately powered RCTs are warranted.
Abstract: To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27–0.67; p = 0.0002; I 2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46–0.88; p = 0.006; I 2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44–1.78; p = 0.72; I 2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27–0.68; p = 0.0002; I 2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38–1.08; p = 0.10; I 2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.

Journal ArticleDOI
TL;DR: High sFlt-1/PlGF ratio in pregnant women is associated with poor pregnancy and neonatal outcomes and timely management for placenta-associated diseases are recommended.
Abstract: Background Soluble fms-like tyrosine kinase receptor-1 (sFlt-1)/placental growth factor (PlGF) ratio has been studied extensively as a predictive marker for pre-eclampsia. However, its usefulness for predicting neonatal outcomes remains unknown. This study aimed to evaluate the association of sFlt-1/PlGF ratio with pregnancy outcomes, neonatal morbidities and short-term postnatal growth patterns in pregnant women and their babies. Methods sFlt-1 and PlGF were measured in women with fetal intrauterine growth retardation (IUGR) or pre-eclampsia during gestational age (GA) of 16–36 weeks. These women were classified into high- and low-ratio groups with a sFlt-1/PlGF cut-off ratio of 85. The maternal and neonatal outcomes were retrospectively reviewed and compared between the two groups. Results A total of 25 pregnant women were recruited. Thirteen of them had a sFlt-1/PlGF ratio over 85 and twelve had a ratio of less than 85. The median duration from elevation of sFlt-1/PlGF to delivery was 4.5 weeks. Women in the high SFlt-1/PlGF ratio group had higher rates of intrauterine fetal demise (2/13 vs. 0/12) and early termination (1/13 vs. 0/12). The surviving offspring in this group had a higher incidence of preterm birth (GA: 31.4 ± 2.9 weeks vs. 37.3 ± 1.3 weeks, p 0.001 ), lower birth weight (1142 ± 472 g vs. 2311 ± 236 g, p vs. 0/12, p = 0.002) and bronchopulmonary dysplasia (4/10 vs. 0/12, p = 0.01). However, the percentile of body weight, height and head circumference at 28 days of age, 56 days of age and the corrected age of 6 months were comparable between groups. Conclusions High sFlt-1/PlGF ratio in pregnant women is associated with poor pregnancy and neonatal outcomes. Therefore, the monitoring of sFlt-1/PlGF ratio in pregnant women with fetal IUGR and timely management for placenta-associated diseases are recommended.

Journal ArticleDOI
TL;DR: The effects of olighydramnios on lung development, the mechanisms of oligohydramnio-induced pulmonary hypoplasia identified in various animal studies, and the long-term respiratory outcomes in childhood of olig carbohydrates-exposed fetuses reported by a population-based study are described.
Abstract: Pulmonary hypoplasia is a substantial cause of death in newborn infants, and oligohydramnios is one of the most commonly associated abnormalities. Lung growth is influenced by physical factors such as the intrauterine space, lung liquid volume and pressure, and fetal breathing movements. During lung development, the main physical force experienced by the lungs is stretching induced by breathing movements and the lung fluid in the airspaces. Oligohydramnios reduces the intrathoracic cavity size, thus disrupting fetal lung growth and leading to pulmonary hypoplasia. The exact mechanism by which oligohydramnios alters the respiratory system structure and the effect of oligohydramnios on long-term respiratory outcomes remain unknown. In this review, we summarize the effects of oligohydramnios on lung development, discuss the mechanisms of oligohydramnios-induced pulmonary hypoplasia identified in various animal studies, and describe the long-term respiratory outcomes in childhood of oligohydramnios-exposed fetuses reported by a population-based study.

Journal ArticleDOI
TL;DR: Persistent inflammation with oxidative DNA damage in the respiratory tract may be a crucial mechanism in BPD.
Abstract: Background Bronchopulmonary dysplasia (BPD) remains the most common complication of very low birth weight (VLBW) preterm infants, and inflammatory regulation plays a role in the development of the BPD. Interleukin-6 (IL-6) has an important role in airway inflammation and therefore can be used as a marker of airway injury. The study aimed to compare the changes between IL-6 and oxidative stress marker with 8-hydroxy-2′-deoxyguanosine (8-OHdG) from serum and tracheal aspiration (TA) in VLBW preterm infants following development of BPD. Methods This birth cohort study enrolled 80 VLBW preterm infants, including 26 who developed BPD. All infants completed the study and survived at 36 weeks postmenstrual age. IL-6 and 8-OHdG concentrations from serum and TA on Day 1 and Day 28 after birth were measured using immunoassay. Results IL-6 and 8-OHdG in serum and TA were higher in the BPD group than in the non-BPD group on the 1 st day after birth ( p th day of life in the BPD group ( p st day ( r = 0.64, p th day of life ( r = 0.76, p Conclusion Persistent inflammation with oxidative DNA damage in the respiratory tract may be a crucial mechanism in BPD.

Journal ArticleDOI
TL;DR: For those with treatment in the intensive care unit because of prolonged loss of consciousness and rescue by a ventilator, special attention should be given and follow-up should be performed to determine whether DNS or PNS occurs, particularly epilepsy and cognitive deficits.
Abstract: Background Carbon monoxide (CO) poisoning is one of the common causes of poisoning in patients and can result in significant morbidity and mortality. However, few studies have focused on the pediatric group. Methods We retrospectively reviewed children (age Results A total of 81 children were enrolled. The annual case number increased from five cases in 2002 to 20 in 2010, particularly during the cold months (December to February). The most common source of exposure was an indoor heating system (54.3%). The most common presenting symptoms were vomiting (32.1%) and consciousness changes (30.9%). HBO treatment tended to be administered to patients with a higher initial COHb (%) ( p p p = 0.002). After multivariate analysis, treatment in the intensive care unit because of prolonged loss of consciousness ( p = 0.002) was the only independent risk factor for patients with DNS; only rescue by a ventilator ( p Conclusion For those with treatment in the intensive care unit because of prolonged loss of consciousness and rescue by a ventilator, special attention should be given and follow-up should be performed to determine whether DNS or PNS occurs, particularly epilepsy and cognitive deficits.

Journal ArticleDOI
TL;DR: Results indicate that for the initiation of corticosteroid therapy, serum [LDH4 + LDH5] level is a more sensitive biomarker than total LDH.
Abstract: Although usually self-limiting, Mycoplasma pneumoniae pneumonia (MPP) may lead to clinical or radiological deterioration despite macrolide antibiotic therapy, resulting in the development of refractory MPP (RMPP). Corticosteroids have been used to treat RMPP with beneficial effects. Serum lactate dehydrogenase (LDH) is a suggested biomarker for the use of steroid therapy. Since serum LDH is a non-specific marker and elevated in many inflammatory processes, this study investigates the predicting level of LDH isoenzymes for RMPP. Fifty-four children with non-refractory M. pneumoniae pneumonia (NRMPP) and 16 children with RMPP were enrolled in this study. In comparison to the NRMPP group, the RMPP group showed significantly higher levels of serum LDH. Concerning LDH isoenzymes, the RMPP group showed significantly lower proportions of LDH1 and LDH2, while higher LDH4 and LDH5 percentage. Receiver operating characteristic curve analysis showed that the area under the curve for the total LDH data was 0.812 with a cut-off of 408 IU/L (sensitivity of 75.0%, specificity of 72.2%). The areas under the curve for LDH4, LDH5, and [LDH4 + LDH5] were estimated to be 0.813, 0.818, and 0.829, respectively. The threshold for [LDH4 + LDH5] was estimated to be 109.4 IU/L (sensitivity, 75.0%; specificity, 87.0%). These results indicate that for the initiation of corticosteroid therapy, serum [LDH4 + LDH5] level is a more sensitive biomarker than total LDH.

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TL;DR: In VLBW preterm infants, EUGR was significantly associated with low MDI scores assessed at a corrected age of 24 months, and was an independent predictor for neurodevelopmental outcomes.
Abstract: Background For infants with very low birth weights (VLBW), their neurodevelopmental outcomes are thought to be associated with extra-uterine growth retardation (EUGR). In this study, based on a single institute, we analyzed the association between different levels or severity of EUGR of VLBW infants and their neurodevelopmental outcomes later at a corrected age of 24 months. Methods This is a hospital-based retrospective cohort study. The severity of EUGR was classified into three categories according to the z-score of discharge weight: z Results In total, 224 VLBW infants were enrolled in this study from 1997 to 2006. In the univariate analysis, EUGR for weight at discharge from hospital was associated with MDI Conclusion In VLBW preterm infants, EUGR was significantly associated with low MDI scores assessed at a corrected age of 24 months. Early evaluation and recognition of EUGR should be emphasized when caring for preterm infants.

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TL;DR: Nesting in the prone position has a pain reducing effect, enhancing comfort and reducing stress in premature infants, and there were insignificant differences in the mean levels of salivary melatonin between the positions.
Abstract: Background Nesting positions are commonly used in procedural analgesic administration in premature neonates. The effectiveness of nesting positions is questioned. The aim of the this study was to assess the pain, stress, comfort and salivary cortisol and melatonin values in nesting positions during the heel lance procedure in premature infants at the NICU. Methods Experimental research; repeated measurement design. The sample comprised 33 premature neonates with gestational age of 31–35 weeks who had been hospitalized in the NICU. Nesting positions were given using linen or towels. The procedure of heel lance was recorded on camera. The camera recordings were evaluated according to the NIPS and the COMFORTneo scale. Saliva samples were obtained five minutes prior to and 30 min after the heel lance procedure. Salivary Cortisol and Melatonin were measured using the Salimetrics Cortisol Elisa Kit and the Salimetrics Melatonin Elisa Kit. Results The crying time, the mean NIPS score, the COMFORTneo score, the COMFORTneo NRS-pain scores and the COMFORTneo NRS-distress scores for premature neonates who were in the prone position during the procedure were significantly lower than the scores in the supine position (p Conclusions Nesting in the prone position has a pain reducing effect, enhancing comfort and reducing stress in premature infants.

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TL;DR: Peritoneal dialysis is an effective route of renal replacement therapy in the neonatal period for management of metabolic disturbances as well as renal failure in patients with a high mortality rate.
Abstract: Background The aim of present study was to evaluate the indications, complications and outcomes of acute peritoneal dialysis (APD) in neonates at a referral university hospital during the previous 8 years. Methods This retrospective analysis included a total of 52 newborn infants who underwent APD in a neonatal intensive care unit between January 2008 and March 2016. Demographic, clinical, laboratory and microbiological data were extracted from patients' medical files. Results The primary causes for requiring APD were acute tubular necrosis (n = 36, 69.2%), inborn error of metabolism (n = 10, 19.2%), congenital nephrotic syndrome (n = 2, 3.9%), bilateral polycystic kidney (n = 2, 3.9%), renal agenesis (n = 1, 1.9%), and obstructive uropathy (n = 1, 1.9%). The mean duration of APD was 8.7 ± 15.87 days (range: 1–90 days). Procedural complications were mainly hyperglycemia (n = 16, 47.1%), dialysate leakage (n = 7, 20.6%), peritonitis (n = 3, 8.8%), catheter obstruction (n = 3, 8.8%), bleeding at the time of catheter insertion (n = 2, 5.9%), catheter exit site infection (n = 2, 5.9%), and bowel perforation (n = 1 2.9%). There were 40 deaths (76.9%), mainly due to underlying causes. Ten of the 12 survivors showed full renal recovery, but mild chronic renal failure (n = 1) and proteinuria with hypertension were seen (n = 1) in each of remaining patients. Conclusion Peritoneal dialysis is an effective route of renal replacement therapy in the neonatal period for management of metabolic disturbances as well as renal failure. Although major complications of the procedure are uncommon, these patients still have a high mortality rate due to serious nature of the underlying primary causes.

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TL;DR: The highest risk for hypoglycemia in early postnatal period was present especially in LPI group, and compliance levels with the AAP guideline was found to be satisfactory.
Abstract: Background Hypoglycemia is low blood glucose level that may negatively affect neurological and developmental prognosis. The American Academy of Pediatrics (AAP), Committee on Fetus and Newborn defined the safe glucose concentrations in the 2011 guideline for newborns at risk for hypoglycemia. This study aimed to investigate the incidence and associated risk factors for hypoglycemia in newborn infants having risk and to assess compliance with the AAP guideline. Methods According to 2011 AAP guideline for hypoglycemia, the newborns at risk for hypoglycemia included in this study were divided to four groups [infant of diabetic mother (IDM), large-for-gestational-age (LGA) infants, small-for-gestational-age (SGA) infants, and late preterm infants (LPI)]. Results Of the 207 newborn infants, there were 12 cases in IDM group (5.7%), 79 cases in LGA group (38.1%), 66 cases in SGA group (31.8%) and 50 cases in LPI group (24.1%). The incidences of hypoglycemia in these four groups were 2 (16.6%), 10 (12.7%), 8 (12.2%) and 17 (34%), respectively. Although the gender, delivery method, birth weight and 5-min Apgar score at 5-min were not found to be associated with hypoglycemia (P > 0.05), lower gestational age was determined to be associated with higher incidence of hypoglycemia (P = 0.02). Median first feeding time was 55 min and time between first nutrition and blood glucose measurement was 30 min in all cases. Conclusion Highest risk for hypoglycemia in early postnatal period was present especially in LPI group. Our compliance levels with the AAP guideline was found to be satisfactory.

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TL;DR: Earlier re-evaluation might be possible when a patient's initial NST-TSH levels and maximal or 2-year LT4 doses are low, as both are important predictors of successful trial-off therapy in CH patients.
Abstract: Background To analyze predictive factors suggesting transient congenital hypothyroidism (TCH) compared to permanent congenital hypothyroidism (PCH) or transient thyroid function test (TFT) abnormalities among children who had positive screening results at our centers over the past decade. Methods A retrospective chart review of 105 subjects who presented elevated TSH levels on a newborn screening test (NST) was done. TCH was defined when a trial-off therapy was successful, and PCH was defined when a trial failed or when the subject was kept on medication beyond 3 years of age. A transient TFT abnormality was defined when follow-up TFTs were normalized without levothyroxine (LT4) therapy. Results Congenital hypothyroidism (CH) was diagnosed in 75.2% (TCH 35.2% and PCH 40.0%) of all subjects; the others (24.8%) showed transient TFT abnormalities. Initial NST-TSH levels (optimal cutoff point, 31.0 μIU/mL), the LT4 dose at 2 years of age (4.1 μg/kg/day), and the maximal LT4 dose (50 μg/day) merged as significant predictive factors discriminating between TCH and PCH. The initial serum level of free T4 (1.06 ng/dL) and not TSH (27.2 μIU/mL) was the only discriminating factor between transient TFT abnormalities and TCH. Conclusion Earlier re-evaluation might be possible when a patient's initial NST-TSH levels and maximal or 2-year LT4 doses are low, as both are important predictors of successful trial-off therapy in CH patients. When the initial serum level of free T4 is above the average value in neonates with mildly elevated TSH levels, TFTs may be more likely to normalize on their own.

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TL;DR: Maternal neutrophil-to-lymphocyte ratio, parity, and birth weight can independently predict the risk of NEC in very preterm infants, whereas clinical and histological chorioamnionitis and funisitis are not predictive of NEC.
Abstract: Background Despite the clinical relevance of necrotizing enterocolitis (NEC), it remains difficult to predict which preterm infants are more likely to develop NEC. Contrary to the neonatal risk factors for the development of NEC, little information is available regarding maternal (prenatal) risk factors. We aimed to identify maternal risk factors associated with the subsequent development of NEC in very preterm infants and to determine whether the placental inflammatory lesions were related to the NEC. Methods This retrospective cohort study examined newborns born at n =354) between July 2003 and July 2014 at a university teaching hospital. Medical records of eligible newborns and their mothers were reviewed. Maternal blood white blood cell and differential counts were measured at admission and the placentas were examined histologically after delivery. The primary outcome measure was NEC Bell Stage≥IIa. Bivariate analyses and multivariate logistic regression were used for the statistical analyses. Results NEC was diagnosed in 26 of 354 very preterm infants (7.3%), including 19 Stage II and seven Stage III infants. Multivariate regression analysis identified maternal neutrophil-to-lymphocyte ratio [odds ratio (OR)=1.08, p =0.002], multiparity (OR=3.41, p =0.013), and birth weight (OR=0.07 per kg increase, p =0.01), but not clinical and histological chorioamnionitis and funisitis as significant predictors of NEC. Conclusion Maternal neutrophil-to-lymphocyte ratio, parity, and birth weight can independently predict the risk of NEC in very preterm infants, whereas clinical and histological chorioamnionitis and funisitis are not predictive of NEC.