Incidence Of Patent Ductus Arteriosus Research Articles

Experiencia con ibuprofeno para el tratamiento de la persistencia de conducto arterioso en un hospital de tercer nivel en la Ciudad de México

IntroductionHaemodynamically significant patent ductus arteriosus increases morbidity-mortality rates in premature newborns. ObjectiveTo determine the incidence of patent ductus arteriosus in our population, as well as the closure rates of success and failure with ibuprofen and other related causes for failure. Materials and methodsA retrospective study was conducted on of 42 patients treated with one or 2 cycles of ibuprofen for patent ductus arteriosus closure from June 2011 to October 2012 at Instituto Nacional de Perinatología, Mexico City. The initial dosage was10mg/kg/day, and 2 additional doses of 5mg/kg/day. ResultsThere were 64 cases out of 295 admissions. Age at diagnosis: 5.0 days (±3.1); age at beginning of treatment: 5.3 days (±5.6). Rate of success for first cycle: 47.7%. If a second cycle was necessary the age at treatment was 9 days (±2.9), the success rate was 42.8% and the failure rate was 57.1%. If surgical closure was necessary, treatment was administered at 19.1 days (±7). Four patients (6%) developed acute renal failure associated with the use of ibuprofen. ConclusionsThere were no statistical differences in the rate of success for the closure of patent ductus arteriosus with the first or second cycle of ibuprofen (47.7% vs 42.8%) (p=1). With ibuprofen dosages actually used, the success rate for the closure of PDA is less with the second cycle than with the first one, but is not significant. There were no differences as regards IV fluids, neonatal sepsis, mechanical ventilation, or diuretics. Starting treatment after the 5th day is associated with an increase in the failure rate.

A RARE CASE OF PATENT DUCTUS ARTERIOSUS WITH EISENMENGER SYNDROME IN ADULT

Patent ductus arteriosus (PDA) is a congenital heart defect in which the ductus arteriosus that typically connects the aorta to the left pulmonary artery fails to spontaneously close after birth. Incidence of PDA is about 6 per 10,000 in full term infants and 1 per 3 in preterm infants. Unrepaired

Single nucleotide polymorphisms in AGTR1, TFAP2B, and TRAF1 are not associated with the incidence of patent ductus arteriosus in Japanese preterm infants

Persistent patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Single nucleotide polymorphisms (SNP) in several genes, including angiotensin II receptor, type 1 (AGTR1), transcription factor AP-2 beta (TFAP2B) and tumor necrosis factor receptor-associated factor 1 (TRAF1), have been reported to be associated with PDA in preterm infants. The aim of this study was to evaluate the relationships between PDA in preterm infants and polymorphisms in AGTR1, TFAP2B and TRAF1 in the Japanese population. The subjects consisted of 107 preterm infants with gestational age <32 weeks. Extremely low-birthweight infants were treated with prophylactic indomethacin during the first 24 h after birth. Five SNP, namely, rs5186 in AGTR1, rs987237 and rs6930924 in TFAP2B, and rs1056567 and rs10985070 in TRAF1, were genotyped using TaqMan SNP genotyping assays. There were no significant differences in the distributions of the genotypes and allele frequencies of all studied SNP between the PDA group (n = 46) and the non-PDA group (n = 61). There were no significant associations between the studied SNP and the incidence of PDA in Japanese preterm infants. These SNP may not be clinically important predisposing factors for PDA in Japanese preterm infants.

Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E&lt;sub&gt;2&lt;/sub&gt;

The incidence of patent ductus arteriosus is known to be higher in premature neonates with infection than in those without infection. However, the detailed mechanism has not been investigated. Lipopolysaccharide (LPS; 100 μg/kg) was injected into timed-pregnant Wistar rats on day 18 and 19 of pregnancy. The fetuses were delivered by cesarean section on gestational day 21. Using a rapid whole-body freezing method, it was found that closure of the ductus arteriosus (DA) was significantly delayed in neonates from LPS-injected rats after birth. Histological analysis demonstrated that there was no difference in vascular remodeling of the DA. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the tumor necrosis factor α and inducible nitric oxide synthase (iNOS) mRNA expression level was significantly increased, but there was no difference in cyclooxygenase 2 and prostaglandin receptor, EP4, mRNA expression in the DA from LPS-injected rats. Moreover, the NOS inhibitor,Nω-Nitro-L-arginine methyl ester hydrochloride, significantly prevented the delayed closure of the DA after birth in neonates from LPS-injected rats. The present study demonstrated that LPS-mediated infection delayed closure of the rat DA without apparent histological changes. iNOS, but not prostaglandin E2, may play a primary role in delayed functional closure of the DA. (Circ J 2016; 80: 703-711).

Mechanical ventilation modes for respiratory distress syndrome in infants: a systematic review and network meta-analysis.

IntroductionThe effects of different mechanical ventilation (MV) modes on mortality outcome in infants with respiratory distress syndrome (RDS) are not well known.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published through April 2014 that assessed mortality in infants with RDS given different MV modes. We assessed studies for eligibility, extracted data, and subsequently pooled the data. A Bayesian fixed-effects model was used to combine direct comparisons with indirect evidence. We also performed sensitivity analyses and rankings of the competing treatment modes.ResultsIn total, 20 randomized controlled trials were included for the network meta-analysis, which consisted of 2,832 patients who received one of 16 ventilation modes. Compared with synchronized intermittent mandatory ventilation (SIMV) + pressure support ventilation (PSV), time-cycled pressure-limited ventilation (TCPL) (hazard ratio (HR) 0.290; 95% confidence interval (CI) 0.071 to 0.972), high-frequency oscillatory ventilation (HFOV) (HR 0.294; 95% CI 0.080 to 0.852), SIMV + volume-guarantee (VG) (HR 0.122; 95% CI 0.014 to 0.858), and volume-controlled (V-C) (HR 0.139; 95% CI 0.024 to 0.677) ventilation modes are associated with lower mortality. The combined results of available ventilation modes were not significantly different in regard to the incidences of patent ductus arteriosus and intraventricular hemorrhage.ConclusionCompared with the SIMV + PSV ventilation mode, the TCPL, HFOV, SIMV + VG, and V-C ventilation modes are associated with lower mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0843-7) contains supplementary material, which is available to authorized users.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

Background:With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.Methods:All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.Results:A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.Conclusions:Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

Acute Kidney Injury in Premature, Very Low-Birth-Weight Infants.

The epidemiology of neonatal acute kidney injury (AKI) is not well established, partly due to lack of a consensus definition. Preterm neonates are likely especially vulnerable to AKI. We performed a retrospective review to assess the incidence of and risk factors for AKI in very low-birth-weight (VLBW), premature infants admitted to a level 4 NICU (2006-2007). AKI was classified using a standardized definition based on changes in serum creatinine (SCr). AKI incidence varied inversely with gestational age (GA): 65% (22-25 weeks), 25% (26-28 weeks), 9% (29-32 weeks) as did severity (p < 0.001). Stage 1 AKI was most common in each cohort. Stages 2 and 3 AKI comprised approximately 60% of AKI in the 22- to 25-week cohort but 20% or less in the older cohorts. By univariate analysis, factors associated with AKI included younger GA, lower BW, lower Apgar scores, hypotension, more frequent treatment with nephrotoxic antimicrobials, longer-duration mechanical ventilation, and higher incidence of patent ductus arteriosus (PDA) requiring treatment. By multiple logistic regression analysis, only GA, hypotension, PDA, and longer duration of mechanical ventilation were independently associated with AKI. AKI was not independently associated with risk of death. Our study suggests that small increases (≥ 0.3 mg/dL) in SCr occur frequently in premature, VLBW infants, and are associated with increased morbidity but not mortality. AKI incidence and severity were highest in the youngest GA cohort. Understanding the epidemiology, risk factors, and impact of neonatal AKI is crucial as long-term premature infant survival continues to improve.

Surgical ligation of patent ductus arteriosus in premature infants: trends and practice variation.

We sought to analyse the variation in the incidence of patent ductus arteriosus over three recent time points and characterise ductal ligation practices in preterm infants in the United States, adjusting for demographic and morbidity factors. Using the Kids' Inpatient Database from 2003, 2006, and 2009, we identified infants born at ⩽32 weeks of gestation with International Classification of Diseases, Ninth Revision diagnosis of patent ductus arteriosus and ligation code. We examined patient and hospital characteristics and identified patient and hospital variables associated with ligation. Of 182,610 preterm births, 30,714 discharges included a patent ductus arteriosus diagnosis. The rate of patent ductus arteriosus diagnosis increased from 14% in 2003 to 21% in 2009 (p<0.001). A total of 4181 ligations were performed, with an overall ligation rate of 14%. Ligation rate in infants born at ⩽28 weeks of gestation was 20% overall, increasing from 18% in 2003 to 21% in 2009 (p<0.001). The ligation rate varied by state (4-28%), and ligation was associated with earlier gestational age, associated diagnoses, hospital type, teaching hospital status, and region (p<0.001). The rates of patent ductus arteriosus diagnosis and ligation have increased in the recent years. Variation exists in the practice of patent ductus arteriosus ligation and is influenced by patient and non-patient factors.

CeasIng Cpap At standarD criteriA (CICADA): predicting a successful outcome.

PBs with a higher GA and Bwt without a PDA ceased CPAP earlier using the CICADA method. Bwt was better than GA for predicting CPAP duration and attempts to cease CPAP. Our previous studies showed that CeasIng Cpap At standarD criteriA (CICADA) significantly reduces CPAP time, oxygen requirements and caffeine use. Some PBs however using the CICADA method required >2 attempts to cease CPAP ('slow CICADA' group). PBs in the 'fast CICADA' group (<3 attempts to cease CPAP) (a) have longer gestational age and higher birth weight, (b) shorter mechanical ventilation and (c) lower incidence of patent ductus arteriosus. Attempts to cease CPAP decreased by 0.5 times per 1 week increase in GA and 0.3 times per 100-g increase in birth weight for PBs <30 weeks gestation.

G137(P) Patent ductus arteriosus of prematurity: to treat or not to treat?: Abstract G137(P) Table 1

Background Incidence of patent ductus arteriosus in neonates is 30–60% depending on the degree of prematurity. Although patent ductus arteriosus is associated with significant morbidity and mortality in preterm infants, there is a wide variation in management of patent ductus arteriosus in preterm infants. Methods We reviewed of our 22 year experience from 1992 to 2013 in all neonates diagnosed with a haemodynamically significant patent ductus arteriosus at the University Hospital of Wales. Haemodynamically significant patent ductus arteriosus is described as: (1) left atrium/aortic ratio of >1.5, (2) significant left heart volume overloading, (3) bounding femoral pulses, (4) hyperactive precordium and (5) persistent ventilator requirements. Results A total of 200 cases were eligible. The results are summarised in the Table 1: Pharmacological treatment = Treatment with either Indomethacin or Ibuprofen Conclusion There were no significant differences in NEC, IVH, CLD or death between treatment and no-treatment group despite the former cases being at lower gestations with lower birth weights. Our result may lend further support towards non-surgical management of patent ductus arteriosus with medication if treatment is not considered to be contraindicated.

Management of patent ductus arteriosus in premature infants.

Patency of the ductus arteriosus is required for fetal survival in utero. In infants born prematurely, ductus fails to close and shunt reverses from left to right. Incidence of patent ductus arteriosus (PDA) is inversely proportional to the gestational age. A large PDA (>1.5 mm diameter) with left to right shunt in very low birth weight infants can cause pulmonary edema, congestive heart failure, pulmonary hemorrhage and increase the risk for bronchopulmonary dysplasia. Attempts to prevent or close the duct by pharmacological or surgical methods have not changed the morbidity or the long term outcome. Pharmacological treatment with indomethacin or ibuprofen is successful in 75 to 80 % of infants but its use also exposes these infants to undesirable side effects like gastrointestinal bleeding, perforation and necrotizing enterocolitis. Prophylactic therapy with indomethacin or ibuprofen to prevent PDA has not altered the morbidity or long term outcome. Currently, there is a dilemma as to how to treat, when to treat and whom to treat. Recent literature suggests a trial of conservative management during the first week followed by selective use of anti-inflammatory drugs. Surgical ligation is reserved for infants who fail medical therapy and still remain symptomatic. Spontaneous closure of the PDA has been reported in up to 40-67 % of very low birth weight (VLBW) infants by 7 d. In this review authors discuss these controversies and propose a more rational approach.

Serum caffeine concentrations and short-term outcomes in premature infants of ⩽29 weeks of gestation.

Caffeine is effective in the treatment of apnea of prematurity but it is not well known if the therapeutic concentration of the drug has an impact on other neonatal outcomes such as chronic lung disease (CLD). The aim of this study was to determine if there is an association between caffeine concentrations and the incidence of CLD in premature infants of ⩽29 weeks of gestation. A retrospective chart review of all the infants born ⩽29 weeks of gestation from 2007 to 2011, who survived until discharge or 36 weeks postmenstrual age, was conducted. Caffeine concentrations were obtained weekly on infants getting the drug. Average caffeine concentrations (ACCs) were determined for the duration of caffeine therapy and correlated with CLD, length of stay (LOS), oxygen at discharge (OD), duration of ventilation (DV) and total charges for hospitalization for each patient. Of the 222 eligible infants, 198 met the inclusion criteria. ACC for infants without CLD was 17.0±3.8 μg ml(-1) compared with infants with CLD 14.3±6.1 μg ml(-1) (P<0.001). Infants receiving high ACC (>14.5 μg ml(-1)) had lower incidence of patent ductus arteriosus, lesser number of days on ventilator and oxygen, lesser need for diuretics, lower incidence of CLD, were more likely to go home without supplemental OD and had lower LOS and lower total hospital charges (all differences were significant P<0.05) Multiple logistic regression modeling after adjusting for confounding variables indicated that higher caffeine concentrations were significantly associated with decrease in CLD. Receiver operating curve analysis confirmed a significant predictive ability of caffeine concentration for CLD with a cutoff concentration of 14.5 μg ml(-1) (sensitivity of 42.6 and specificity of 86.8). The AUC (area under the curve) for the prediction of CLD was 0.632 (95% confidence interval 0.56-0.69, P=0.009). Caffeine concentrations >14.5 μg ml(-1) were strongly correlated with reduced CLD in infants born at ⩽29 weeks of gestation. Higher caffeine concentrations were associated with decreased total hospital charges, DV, OD and LOS. Additional randomized trials are needed to confirm these findings, to identify ideal serum concentrations and determine possible long-term neurologic benefits.

A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2

Objective: Numerous investigations have demonstrated that phototherapy (PT) directly or indirectly causes ductal patency by photorelaxation effect. In this observational study, we aimed to assess the effect of PT on the incidence of patent ductus arteriosus (PDA) together with prostaglandins (PGE2) and (PGI2) levels in preterm infants.Methods: Preterm infants whose gestational age < 34 weeks and who required PT in the first 3 d of life were enrolled in this prospective study. The clinical signs of PDA, the data of detailed echocardiographic study were recorded and plasma PGE2 and PGI2 levels were measured before and after PT. The outcome measures were the status of ductus arteriosus and alterations of PGE2 and PGI2 levels under the effect of PT.Results: A total of 44 preterm infants were enrolled in the study, of these 21 (47.7%) were in Group 1 (Non-PDA Group) and 23 (52.3%) were in Group 2 (PDA Group). After PT, ductal reopening occurred in three infants (14.3%) in Group 1, while ductus closed in four infants in Group 2 (17.3%). PT does not seem to effect ductal patency for both groups (p = 0.250 and p = 0.125, respectively). PGE2 levels were not different before and after PT for both groups (p = 0.087, p = 0.408, respectively). However, PGI2 levels were significantly decreased after PT in both groups (p = 0.006, and p = 0.003, respectively).Conclusion: There was no effect of PT on ductal patency. We can conclude that PGs were eliminated simultaneously with ductal closure and photorelaxation effect did not influence PG levels.

Características clínicas e ecocardiográficas associadas à evolução do canal arterial em recém-nascidos com peso de nascimento inferior a 1.500g

ABSTRACTObjective:To identify clinical and echocardiographic parameters associated with the evolution of the ductus arteriosus in neonates with birth weight lower than 1,500g.Methods:Retrospective study of 119 neonates in which clinical parameters (Prenatal: maternal age, risk of infection and chorioamnionitis, use of corticosteroid, mode of delivery and gestational age. Perinatal: weight, Apgar score, gender and birth weight/gestational age classification; Postnatal: use of surfactant, sepsis, fluid intake, heart murmur, heart rate, precordial movement and pulses, use of diuretics, oxygenation index, desaturation/apnea, ventilatory support, food intolerance, chest radiography, renal function, hemodynamic instability, and metabolic changes) and echocardiographic parameters (ductus arteriosus diameter, ductus arteriosus/weight ratio, left atrium/ aorta ratio, left ventricular diastolic diameter, and transductal flow direction, pattern and velocity) were analyzed. The clinical and echocardiographic parameters analyzed were considered statistically significant when p<0.05.Results:In the 119 neonates, the incidence of patent ductus arteriosus was 61.3%; 56 received treatment (46 pharmacological and 10 surgical treatment), 11 had spontaneous closure, 4 died, and 2 were discharged with patent ductus arteriosus. A higher incidence of chorioamnionitis, use of surfactant, lower weight and gestational age, sepsis, heart murmur, ventilatory support and worse oxygenation indices were observed in the neonates receiving treatment. The group with spontaneous closure had a smaller ductus arteriosus diameter, lower ductus arteriosus/weight ratio, and higher transductal flow velocity.Conclusion:Based on clinical and echocardiographic parameters, the neonates with spontaneous closure of the ductus arteriosus could be differentiated from those who required treatment.

Perinatal risk factors for adverse long‐term pulmonary outcome in premature infants: Comparison of different definitions of bronchopulmonary dysplasia/chronic lung disease

The aim of the study was to determine factors that affect adverse long-term pulmonary outcome in premature infants. This retrospective analysis was done using 306 clinical records of preterm singleton neonates at <32 weeks of gestation. Two definitions of adverse pulmonary outcome were used: chronic lung disease (CLD), defined as a need for supplemental oxygen for at least 28 days after birth; and bronchopulmonary dysplasia (BPD), defined as oxygen dependency for at least 28 days after birth plus at 36 weeks postmenstrual age and/or a need for positive-pressure ventilatory support. Selected perinatal variables were compared between these definitions, and factors related to disease development were identified on multivariate analysis. The incidence of CLD and of BPD were 42% and 17%, respectively. Regardless of the definitions, the incidence of patent ductus arteriosus and of neonatal infection were significantly higher in the patients who met the disease criteria, but that of chorioamnionitis and of small for gestational age (SGA) were significantly higher in the patients only when the BPD definition was applied. Multivariate analysis identified SGA as an independent risk factor for the development of BPD after controlling for gestational age. Among selected perinatal variables, prenatal risk factors, particularly SGA, contributed to prolonged dependency on oxygen and/or positive-pressure ventilatory support, in combination with neonatal risk factors.

Évolution néonatale précoce des nouveau-nés prématurés de moins de 32 semaines d’aménorrhée ayant une TSH plasmatique supérieure à 10 mUI/L

Thyroid hormones are involved in the development of human vital functions, especially in preterm infants. Hypothyroidism may have consequences in cardiac, respiratory, digestive, and neurological outcomes in this population. The main objective of this study was to evaluate neonatal morbidity in preterm newborns less than 32 weeks of gestation (WG), according to their thyroid stimulating hormone (TSH) rate. Secondly, we assessed the value of a treatment with synthesis thyroid hormones. In a retrospective study, two groups were compared as to whether they had a TSH rate higher or lower than 10 mIU/L. A second analysis was performed to evaluate the advantages of a treatment with L-thyroxine. Perinatal data and morbidity (hemodynamic support, respiratory failure, digestive and neurological functions) were evaluated. From January 2006 to September 2011, 274 newborns under 32 WG were screened. Twenty-five newborns had a TSH rate greater than 10 mIU/L and were matched with 25 preterms having a TSH rate under 10 mIU/L. The incidence of patent ductus arteriosus was significantly higher in the group with TSH over 10 mIU/L (22 vs 6; P<0.001). In the group with TSH over 10 mIU/L, 13 newborns were treated. These were more oxygen-dependent at 28 days of life (7 vs 3; P=0.03) and were full fed later (14 days; 5.5 vs 12 days; 2; P=0.05). A TSH rate higher than 10 mIU/L was associated with a higher incidence of patent ductus arteriosus in preterm newborns under 32 WG. Thyroid synthesis treatment does not improve respiratory or digestive short-term outcome.

Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year retrospective cohort study

Probiotic therapy has been shown to reduce morbidity and mortality of necrotizing enterocolitis (NEC) in premature infants in several international studies using various probiotic agents. The purpose of this study(*) is to describe our experience of using probiotic therapy in preventing NEC in infants with very low birth weight (VLBW) in a neonatal intensive care unit (NICU) and to evaluate whether our records provide evidence of effectiveness for probiotic therapy. In a retrospective cohort study, the efficacy of probiotic therapy in preventing NEC in VLBW infants was investigated via chart review. A probiotic administration protocol using a three-strain (Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement was implemented in August 2007. Patients admitted to the NICU from August 2003 through July 2011 were screened. Primary outcomes are the morbidity and mortality of NEC. The secondary outcomes were severity of NEC and incidence of where infant feeds were stopped but NEC was not diagnosed (NEC scare). There was a significant increased baseline risk of NEC development in the probiotics group, including younger gestational age, higher incidence of patent ductus arteriosus (PDA) and use of indomethacin. The incidence of NEC is similar between the control group (2·8%) and probiotics group (2·4%) (hazard ratio, 1·15; 95% confidence interval [CI], 0·42, 3·12). Mortality of NEC is also not statistically different. Incidence of NEC scare was decreased from 2·8% in control group to 1·4% in probiotics group, although the difference was not statistically significant (P=0·38). Our findings suggest that probiotics are safe in NEC prevention in VLBW infants. We had no cases of infection related to the strains of bacteria used in our product. With the low incidence of NEC (2·8%) and NEC scare (2·8%) in our cohort, we do not have enough power to detect any change in outcome, particularly as our study was observational. However, it is hoped that our data give useful information for others on probiotic prophylactic therapy in the routine clinical management of VLBW infants.

Histological Chorioamnionitis: Effects on Premature Delivery and Neonatal Prognosis

Chorioamnionitis is closely related to premature birth and has negative effects on neonatal morbidity and mortality. In this prospective study, 43 mothers who delivered earlier than 35 gestational weeks and their 57 infants were evaluated clinically and with laboratory findings. Placentas and umbilical cords were investigated histopathologically for chorioamnionitis and funisitis. The overall frequency of clinical and histological chorioamnionitis (HCA) was 8.3% and 23.2%, respectively. The frequency of HCA was 47.3% and 83.3% in mothers delivered <32 weeks and <30 weeks, respectively. Maternal demographic and clinical findings and also leukocyte and C-reactive protein values were not indicative of HCA. Infants of mothers with HCA had significantly lower Apgar scores together with higher SNAP-PE-II and CRIB scores. These infants had increased mechanical ventilator and surfactant requirements, higher incidences of patent ductus arteriosus, early sepsis, and bronchopulmonary dysplasia, and higher mortality rates. The effect of HCA on neonatal morbidity and mortality was more prominent than the effect of low birthweight and lower gestational age. Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

Response to Dr Egan’s letter

Thank you for the opportunity to respond to the letter from Dr Edmund A Egan, Chief Medical Officer of ONY, Inc., manufacturer of Infasurf (Calfactant, (CA)). In the letter by Dr Egan, he refers to the studies presented as abstracts in 2007 (ref. 1,2 in his letter) and our study published electronically as a peer reviewed manuscript in 2011 and included in this print issue. These are different studies, in which different protocols, different timeframes (abstract 2007: Jan 2003 to June 2006; full publication 2011:Jan 2005 to Dec 2009) different infants, different number of patients and different statistical models were used. Dr Egan discusses the increased length of stay (LOS) resulting from improvement in mortality due to surfactant therapy in studies comparing surfactant vs placebo. Based on evidence, the introduction of surfactant therapy has led to significantly decreased mortality and morbidity without increasing resource utilization. The statements of Dr Egan regarding inverse correlation between mortality and LOS are based on a very old study (ref. 3 in his letter) comparing surfactant with placebo in a different ‘era’ of neonatology, where respiratory distress syndrome (RDS) was the major cause of death and had a major influence on LOS. Most important is the fact that surfactant therapy compared with placebo has shown decrease in cost both in infants who survived as well as in infants who died. Subsequent studies on resource utilization are clearly different and these have reported LOS in patients who received one of the three animal-derived surfactants.1, 2 Baroutis et al.3 reported decreased mortality and significantly shorter LOS with poractant alfa (PA), when compared to alveofact or beractant (BE) in a randomized, controlled trial. Fujii et al.4 reported a nonsignificant decrease in mortality (8 vs 19%) and shorter LOS in a PA-treated group compared with that in the BE-treated group (87 vs 97 days, P=0.179). In two randomized, controlled trials comparing PA and BE, incidence of patent ductus arteriosus (PDA), as well as the need for medical or surgical ligation of PDA, were significantly less in patients treated with PA,4, 5 which might therefore contribute to shorter LOS. In a study comparing high vs low dose surfactant therapy, LOS was shorter in the high dose group when compared with low dose group (82 vs 99 days).6 A recently published systematic review and meta-analysis,7 demonstrated a good correlation between higher surfactant efficacy (mortality reduction) and reduced LOS with poractant alfa (PA). Indeed, in the meta-analysis, PA was associated with both a significant reduced risk of death vs BE (P=0.02) and a significantly shorter LOS (weighted mean difference: −26.3 [95% CI: −36.5 to −16.07]; P<0.00001). In the most recent randomized trial comparing PA with BE, LOS was not increased in PA group despite a 50% reduction in mortality rate in the PA-treated group (9.8 vs 20%).8

Value of N-terminal pro-brain natriuretic peptide on evaluating heart failure in neonates with respiratory distress syndrome

Objective To explore the value of plasma N-terminal pro-brain natriuretic peptide(NT-proBNP) in diagnosing or excluding concurrent heart failure (HF) in neonates with respiratory distress syndrome (RDS). Methods One hundred and fifteen preterm infants with RDS, admitted to Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from Jan.2011 to Oct.2012, were classified into 2 groups: HF group (56 cases) and non-HF group (59 cases). Differences in cardiac biomarkers and parameters of ultrasonic cardiogram for cardiac function between the 2 groups were analyzed within 24 hours after birth through univariate factors.To evaluate independent factors for HF, logistic regression analysis was performed including significant univariate factors.Receiver operator characteristic curve (ROC) was used to determine the best cutoff for diagnosis of HF with sensitivity and specificity of more than 90%. Results The level of plasma troponin and CK-MB showed no significant difference between the 2 groups(all P>0.05). Compared with the non-HF group, the incidence of patent ductus arteriosus, patent foramen ovale and pulmonary hypertension, as well as plasma NT-proBNP level and pulmonary artery pressure were significantly higher in the HF group(all P<0.05). In contrast, left ventricular ejection fraction and E/A ratio were significantly lower in the HF group(all P<0.05). Logistic regression analysis, which was performed using the 7 significant univariate factors, showed that only plasma NT-proBNP was the independent factor for evaluating HF(OR=1.359, P=0.000). The area under ROC for NT-proBNP levels for diagnosis of HF in RDS neonates was 0.997 (95% CI 0.962-1.000, P=0.000). A cutoff value of at least 16 379 ng/L had a sensitivity of 91.1% and specificity of 98.3%.All the 8 neonates who died had a plasma NT-proBNP level of 35 000 ng/L in 24 hours after birth, significantly higher than that in survival neonates(P=0.000). Conclusions Plasma NT-proBNP level proved to have the value for independently determining or excluding HF in RDS neonates, and dynamic observation for NT-proBNP level may be used for early prediction of mortality risk in neonates with HF. Key words: Respiratory distress syndrome; N-terminal pro-brain natriuretic peptide; Heart failure; Diagnosis