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Background: Earlier studies on the use of inhaled nitric oxide (iNO) for premature infants born at <34 weeks of gestation requiring respiratory support did not provide conclusive evidence of benefit. National guidelines generally discouraged the use in this population. More recent national guidelines endorsed the use of iNO in premature infants with hypoxic respiratory failure (HRF) associated with persistent pulmonary hypertension of the newborn (PPHN). Recent Studies: Two recently published observational studies evaluated the effect of administering iNO on oxygenation in the first week of life. These studies compared premature infants born at the gestational age (GA) of <34 weeks with HRF associated with PPHN to term and late preterm infants born at the GA of ≥34 weeks who received iNO. Both studies showed a similar effect of iNO on oxygenation in the two infant cohorts. The response rate in the premature infant cohort was 59% in the first study and 90% in the second. The mean response time was 9.2 h and 10.3 h, and the mean duration of therapy was 3.5 days and 8.2 days, respectively. Conclusion: The results of these studies support a trial of iNO in premature infants with persistent hypoxia despite optimum respiratory support. Obtaining a timely echocardiogram to exclude cardiac diseases and diagnose PPHN is logistically challenging for many clinicians, thus, a clinical diagnosis of PPHN might have to be made in these situations. Questions remain regarding the optimum dose of iNO and the duration of the initial iNO trial in these patients. In the most recently published studies, the improvement of oxygenation in iNO-treated infants born at <34 weeks of gestation with HRF and PPHN physiology was as effective as in infants born ≥34 weeks. These studies provide evidence supporting a trial of iNO in the subpopulation of premature infants with HRF associated with PPHN. [ABSTRACT FROM AUTHOR]

Objectives: (1) To investigate whether neonates with perinatal asphyxia and therapeutic hypothermia more often developed PPHN compared to a control group with perinatal asphyxia not treated with hypothermia; (2) To identify risk factors for severe PPHN during hypothermia and evaluate short-term outcome. Methods: This single-center retrospective cohort study included (near-)term neonates with perinatal asphyxia admitted between 2004 and 2016. Neonates with perinatal asphyxia and hypothermia were compared to a historical control group without hypothermia. Primary outcome was PPHN, defined as severe hypoxemia requiring mechanical ventilation and inhaled nitric oxide, confirmed by echocardiography. Short-term adverse outcome was defined as mortality within one month and/or severe brain injury on MRI. Results: Incidence of PPHN was 23% (26/114) in the hypothermia group and 11% (8/70) in controls. In multivariate analysis, PPHN was 2.5 times more common among neonates with hypothermia. Neonates developing PPHN during hypothermia often had higher fraction of inspired oxygen at baseline. PPHN was not associated with a higher risk of severe brain injury. However, early mortality was higher and three infants died due to severe refractory PPHN during hypothermia. Conclusions: In this study PPHN occurred more often since the introduction of therapeutic hypothermia. This was usually reversible and did not lead to overall increased adverse outcome. However, in individual cases with PPHN deterioration occurred rapidly. In such cases the benefits of hypothermia should be weighed against the risk of a complicated, fatal course. [ABSTRACT FROM AUTHOR]

Introduction The prevalence of persistent pulmonary hypertension of newborn (PPHN) has been estimated 1.9/1000 live births. Although the efficacy of inhaled nitric oxide and extracorporeal membrane oxygenation in PPHN is well established but it is difficult to administer and monitor in resource limited countries. Owing to this, other treatment options need to be evaluated. Method This is a prospective observational study conducted in the Pediatric Cardiology Department, NICVD, Karachi, from February 2020 to October 2020 after the approval from the Institutional Ethical Review Committee. All the neonates referred to our Unit were screened by echocardiography (echo) and those who fulfilled the inclusion criteria were included. Echo were done before starting sildenafil and after 72 h to assess the pressure gradient across tricuspid valve and right to left or bidirectional shunt across patent ductus arteriosus, patent foramen ovale, or both. Sildenafil was started with a dose of 1 mg/kg/dose thrice a day and increased to 2 mg/kg/dose after 48 h if partial pressure of oxygen (PO1] did not increase. In neonates who did not respond to increased dose of Sildenafil were added on oral Bosentan 1 mg/kg/dose twice a day. Results Total 82 newborns were enrolled. Fifty-two patients improved after 48 h so were continued on same treatment. Sildenafil dose was increased in 30 (37.9%) patients whose PO2 did not increase to at least 10% from baseline after 48 h of starting treatment. Three patients expired within 48–72 h. Out of 27 remaining patients, only four responded whereas 23 patients did not show any improvement. In these patients, Bosentan was supplemented along with sildenafil. Conclusion The results of our study show effectiveness of oral Sildenafil in treating PPHN. The overall improvement observed in the patients was overwhelming. Combination of Sildenafil with Bosentan is beneficial in patients who did not respond on Sildenafil alone. [ABSTRACT FROM AUTHOR]

Although shown to reduce death or disability in moderate-to-severe hypoxic ischaemic encephalopathy (HIE), therapeutic hypothermia (TH) has recently been associated with an increase in adverse events in low- and middle-income countries (LMIC). To determine the clinical characteristics, complications and short-term outcome in neonates receiving TH in King Edward Memorial Hospital, Mumbai, India. A retrospective single-centre study of neonates with moderate-to-severe HIE who received TH from 1 January 2018 to 31 December 2021 was undertaken. TH was provided as per the unit's protocol using either a servo-controlled device or a phase-changing material (PCM). One hundred and fifty-five neonates were included with 94.2% intramural births. Mean gestation and birthweight were 38.6 (1.5) weeks and 2776.7 (431) g, respectively. HIE staging was moderate in 87.1% and severe in 12.9%, with a mean cord pH of 6.93 (0.14) and seizures in 38.7%. Adverse events included shock (50.3%), clinically significant bleeding (16%), acute kidney injury (6.7%), culture-positive sepsis (11.6%), persistent pulmonary hypertension (9%), bradycardia (9%), food intolerance (14.9%) and premature termination (7.1%). A servo-controlled device (15.5%) or PCM (84.5%) was used, with comparable adverse events. 84.5% of the neonates were discharged, 7.1% discharged against medical advice and 8.4% died. Detailed neurological assessment at discharge/discharge against medical advice suggested neurological impairment in 128 (87.1%) neonates. Adverse events during TH range from asymptomatic laboratory abnormalities to life-threatening complications, which are manageable in well equipped units. Neurological impairment at discharge in neonates who received cooling mandates strict neurological follow-up. Abbreviations: aEEG: amplitude-integrated EEG; AKI: acute kidney injury; BW: birthweight; EEG: electro-encephalogram; GA: gestational age; HELIX: hypothermia for encephalopathy in low- and middle-income countries; HIE: hypoxic ischaemic encephalopathy; IVH: intraventricular haemorrhage; LMIC: low- and middle-income countries; NICHD: National Institute of Child Health and Human Development; NICU: neonatal intensive care unit; PPHN: persistent pulmonary hypertension of newborn; PCM: phase-changing material; SGA: small-for-gestational age; TH: therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

To describe the clinical outcomes following treatment with vasopressin for a sub-cohort of critically ill preterm neonates who have refractory persistent pulmonary hypertension of the newborn (PPHN). Case series Tertiary neonatal intensive care unit, Toronto, Canada. Neonates born <37 weeks gestational age (GA) who received vasopressin for refractory PPHN (lack of response to inhaled nitric oxide) over a 4-year period. Changes in physiological indices of cardio-pulmonary stability during vasopressin therapy were analyzed using one-way repeated measures ANOVA, compared to pretreatment values. Data regarding survival to discharge and neurodevelopmental outcomes at 18–24 months were described. Thirteen neonates with a mean GA of 31.4 ± 3.3 weeks were included. Vasopressin was initiated at 28.5 ± 4.5 h of age. Overall, oxygenation and hemodynamic variables improved significantly following vasopressin therapy (p <.05 at 24 h vs. pretreatment). Oxygenation failure resolved in 8 cases, of which 7 patients survived (6 without disability). Among the 5 cases where oxygenation failure persisted despite vasopressin, 4 died while one survived with disability. Vasopressin offers promise as a therapy for preterm neonates with refractory PPHN and hemodynamic instability, but prospective investigation is needed. [ABSTRACT FROM AUTHOR]

Introduction: Persistent pulmonary hypertension of the newborn (PPHN) is a rapidly increasing condition among neonates. It represents failure of adaptation of pulmonary circulation to the extrauterine environment causing severe hypoxemia in affected newborns. Few data have weighed the relationship of ventricular dysfunction in the context of PPHN and the outcome in involved patients. The aim of this paper is to study ventricular functions in newborns with PPHN and to determine whether short-term outcome is closely related or not to ventricular dysfunction occurring in PPHN.Methods: Thirty full-term neonates with PPHN were screened with conventional echocardiography and tissue Doppler imaging (TDI) for the assessment of ventricular functions at the start of treatment for PPHN, demographic data and Arterial blood gazes were performed as well. The echocardiographic data were compared to healthy age-matched controls. The sensitivity and specificity of relevant echocardiographic data to predict the short-term (Day 3) outcome of patients were measured.Results: Patients with PPHN had both left ventricular (LV) and right ventricular (RV) dysfunction when compared to controls, RV Tei (Cases: 0.39 ± 0.1 versus controls: 0.29 ± 0.08, p < .01) LV Tei (Cases: 0.3 ± 0.04 versus controls: 0.25 ± 0.02, p < .01), LV functions were found of greatest prediction of negative outcome in cases with PPHN than RV Tei.Conclusion: The aforementioned findings are sight opening towards the importance of LV dysfunction in PPHN, LV dysfunction might occur in PPHN as a result of RV-LV interactions and the observed involvement might be an important aggravating factor of PPHN. [ABSTRACT FROM AUTHOR]

Objective: To determine the risk factors and outcomes of persistent pulmonary hypertension of the newborn (PPHN)-associated pneumothorax (PTX).Study design: The medical records of infants diagnosed with PPHN with or without PTX from January 2012 to July 2017 were retrospectively reviewed.Results: Of the 102 included PPHN infants, PTX was found in 32 (31.4%) infants with 43.8% (14/32) mortality. PTX was significantly associated with increased mortality with an odds ratio (OR) of 5.27 (95% confidence interval [CI] 1.96-14.17). Unilateral PTX was more common than bilateral PTX (53.1 versus 46.9%, respectively). Multivariate logistic regression analysis indicated that a 1-minute Apgar score of ≤7 was associated with an increased risk for PTX (adjusted OR = 2.67 [95% CI 1.14-6.25]). In subgroup analysis, each increase of maximum peak inspiratory pressure (PIP) of 1 cmH2O significantly increased the odds of PTX by 1.46 (95% CI 1.02-2.07), while each 1 mmHg increase in arterial partial pressure of oxygen (PaO2) decreased the odds of PTX (adjusted OR = by 0.98 [95% CI 0.97-0.99]).Conclusions: PTX was significantly associated with higher mortality in PPHN infants. Lower Apgar score and increasing PIP in conventional mechanical ventilation were risk factors for PTX. Higher PaO2 was associated with a decreased rate of PTX. [ABSTRACT FROM AUTHOR]

Introduction:Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening neonatal condition, mostly treated with inhaled nitric oxide (iNO), intravenous prostaglandins, oral bosentan, sildenafil and tadalafil. However, the utility of non-oral agents is limited in PPHN for their side effects and inconvenient deliveries. Therefore, oral agents such as bosentan, sildenafil and tadalafil are becoming appealing for their satisfactory efficacy, easy mode of administration and acceptable side effects. Areas covered: We conducted a comprehensive search on Pubmed, Scopus, Web of Sciences concerning the use of bosentan, sildenafil and tadalafil to treat PPHN and summarized their efficacy, safety and pharmacokinetics. Expert opinion: Current randomized controlled trials (RCTs) have demonstrated the favorable responses and tolerable side effects of bosentan and sildenafil. Nevertheless, those RCTs are small and only one study has described the pharmacokinetics of sildenafil in neonates. Accordingly, bosentan, sildenafil and tadalafil remain off-label in clinical use. More well-designed RCTs with large samples and long-term follow-up and pharmacometrics studies are needed to demonstrate the efficacy, safety and pharmacokinetics of bosentan, sildenafil and tadalafil in PPHN. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between changes in brain natriuretic peptide (BNP) and echocardiographic features in persistent pulmonary hypertension of newborn (PPHN).Patients and methods: A total of 76 patients with PPHN treated in our hospital from March 2017 to February 2018 were divided into mild group (n = 33), moderate group (n = 22) and severe group (n = 21) according to the pulmonary arterial systolic pressure, and they were compared with 30 normal newborns (control group) during the same period. All newborns underwent echocardiography, the BNP level was detected, and the correlation between echocardiographic features and BNP changes was analyzed.Results: The BNP level in control group was significantly lower than those in PPHN groups, and it was constantly increased from mild group to severe group (p<.05). There were no significant differences in left atrial diameter (LA) and left ventricular diameter (LV) among groups (p>.05), while there were significant differences in the right atrial diameter (RA), right ventricular diameter (RV) and peak velocity of tricuspid regurgitation (VTR) (p<.05). BNP had no correlations with LA and LV (p>.05), but had positive correlations with RA, RV and VTR (r = 0.527, 0.503 and 0.524, p<.05).Conclusion: The BNP level of patients with PPHN increases with the increasing severity of disease. BNP has close correlations with echocardiographic features of neonatal patients. Predicting the BNP changes via echocardiography is of certain value in guiding the clinical treatment. [ABSTRACT FROM AUTHOR]

Objectives: To explore the incidence, etiologies, diagnostic methods, treatment options and outcomes in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to identify mortality risk factors in a study from six Asian countries.Methods: A retrospective chart review of patients with documented PPHN from seven centers in six Asian countries (Japan, Kuwait, India, Pakistan, Singapore, and Thailand) between 1 January, 2014 and 31 December, 2016, was performed.Results: A total of 369 PPHN infants were identified. The incidence of PPHN ranged from 1.2 to 4.6 per 1000 live births. The all-cause mortality rate was 20.6% (76 of 369). Meconium aspiration syndrome was the primary cause of PPHN (24.1%). In most cases (84.8%) echocardiography was used to establish the diagnosis of PPHN. Sildenafil was the most commonly used pulmonary vasodilator (51.2%). Multivariate multiple regression analysis indicated gestational age <34 weeks (adjusted odds ratio (OR) = 3.27; 95% CI 1.56-6.74), congenital diaphragmatic hernia (CDH)/lung hypoplasia (LH) (adjusted OR = 6.13 (95% CI 2.28-16.42)), treatment with high frequency oscillation ventilation (HFOV) with or without inhaled nitric oxide (iNO) (adjusted OR = 3.11 (95% CI 1.52-6.34)), and inotropic agents (adjusted OR = 9.43 (95% CI 2.71-32.83)) were independently associated with increased risk of death.Conclusions: The incidence of PPHN in the current study was higher than in western settings. Birth weight, gestational age, CDH/LH, HFOV/iNO, and inotropic agents were significant mortality risk factors. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) in preterm neonates is becoming an increasingly recognized morbidity in the neonatal intensive care unit neonatal intensive care unit (NICU), yet its epidemiology, delineation and relation to numerous toxic exposures and common morbidities such as systemic hypertension is just evolving. With a frequency of the patent ductus arteriosus (PDA) as high as 70% in preterm infants born before 28-week gestation, the role of the hemodynamically significant PDA (hs-PDA) remains unclear. Objective: To determine if AKI and systemic hypertension is more common in extremely low gestational age newborns (ELGAN) with hs PDA compared to ELGAN with no or non-hs PDA using modified AKIN and Neonatal Risk, Injury, Failure, Loss of Kidney Function, and End-stage (N-RIFLE) scoring systems. Methods: This was a retrospective cohort study of infants ≤28 weeks gestational age born between 2010 and 2016 who had echocardiographic PDA evaluation completed for hemodynamical significance as well as serial serum creatinine and urine output measurement documented, needed for the two AKI scoring systems: modified AKIN (based on serial serum creatinine) and N-RIFLE (using urine output data). Blood pressure measurements and therapy were evaluated during the hospitalization and on the day of NICU discharge. Baseline characteristics and outcome variables were compared between the hs-PDA and no or non-hs PDA using unpaired t-tests for continuous variables and chi square tests for categorical data. Results: One hundred fifty-one infants were eligible of which 110 had hs-PDA. Infants with hs-PDA were smaller (777 versus 867 g, p = .026), less mature (25.8 versus 26.4 weeks, p = .023) and had greater exposure to nephrotoxic drugs (14 versus 9.4 days, p = .001). Other clinical and demographic variables were similar between the two groups. The overall incidence of AKI was not different between the hs-PDA and no PDA or non-hs PDA groups when evaluated by the acute kidney injury network (AKIN) or N-RIFLE staging; however, preterm newborns with hs-PDA demonstrated a trend towards increased risk of AKI injury (12.7 versus 0.02%, p = .06). The N-RIFLE and AKIN scoring systems demonstrated very poor degree of agreement (kappa = 0.00853) in our study. There was no difference in the rates of hypertension during the hospitalization as well as on the day of NICU discharge. Conclusion: Preterm neonates with hs-PDA had similar rates of AKI and hypertension as neonates with no or non-hs PDA. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk factors and predictors of severity associated with meconium aspiration syndrome (MAS) in the patients admitted to the neonatal intensive care unit (NICU).Materials and Methods: Retrospective study including newborns admitted, between 2005 and 2015, with a diagnosis of MAS.Results: Of the newborns admitted to the NICU, 0.66% were diagnosed with MAS. These had higher prevalence of caesarean delivery (p < .001), nonreassuring or abnormal cardiotocography (CTG) (p < .001), intrapartum maternal fever (p = .002), Apgar scores at the first minute <7 (p < .001) and need of endotracheal intubation at birth (p < .001). Newborns with severe MAS had higher median reactive C protein (86.9 versus 9.65, p = .001) and 73.3% had pulmonary hypertension (p = .027). They required significantly more days of oxygen therapy, mechanical ventilation, nitric oxide, inotropic, and surfactant therapy, as well as longer hospital stay.Conclusions: Nonreassuring or abnormal CTG and low Apgar score at the first minute were established as risk factors for MAS and need of surfactant therapy as a predictor of severity. [ABSTRACT FROM AUTHOR]

Objective: To better understand the impact of persistent pulmonary hypertension (PPHN) on brain oxygenation in term asphyxiated newborns treated with hypothermia. Methods: The regional cerebral oxygenation saturation (rSO2) measured by near-infrared spectroscopy was compared to pre/post-ductal oxygen saturation and mean arterial blood pressure in three term asphyxiated newborns with documented PPHN during their first 4 days of life while they were being treated with hypothermia. Results: The cerebral oxygen saturation remained relatively stable when oxygen saturation was more than 92% and when there was no difference between pre- and post-ductal oxygen saturations. Episodes of desaturations with a difference between pre- and post-ductal saturations, as well as episodes of hypotension, caused a significant decrease in rSO2 in these newborns. Conclusion: This case series demonstrates that PPHN has a profound impact on brain oxygenation in term asphyxiated newborns treated with hypothermia during the first days of life after birth. PPHN may represent an additional risk factor for brain injury in these newborns during the first days of life. [ABSTRACT FROM AUTHOR]

Objectives: To describe the clinical characteristics, diagnostic methods, treatment modalities, and complications, and identify the mortality risk factors, of infants with short-term persistent pulmonary hypertension of the newborn (PPHN).Methods: The clinical data of infants diagnosed with PPHN at Hat Yai Hospital from January 2010 to February 2014 were retrospectively reviewed. Cox proportional hazard regression analysis was performed to assess factors associated with mortality.Results: The records of 119 infants were analyzed. Of these, 47 died giving an in-hospital mortality rate of 39.5%. The prevalence of PPHN (based on inborn births) was 2.8 per 1000 live births. The mean gestational age and birth weight were 39.1 ± 1.6 weeks and 3044 ± 563 g, respectively. Multivariate Cox regression analysis indicated that pneumothorax [adjusted hazard ratio (HR) = 2.07 (95% CI 1.09-3.93)] and acute kidney injury [adjusted HR = 2.99 (95% CI 1.59-5.61)] were factors associated independently with an increased risk for death, while infants who received total parenteral nutrition [adjusted HR = 0.22 (95% CI 0.10-0.50)] had lower mortality.Conclusion: A high mortality rate of PPHN was observed in this study. Significantly higher mortality was noted in infants complicated with pneumothorax and acute kidney injury. [ABSTRACT FROM AUTHOR]

Aim: To study the prevalence of persistent pulmonary hypertension (PPHN) in newborn with meconium aspiration syndrome (MAS) in western Rajasthan, India.Material and Methods: Hundred full-term newborns who had features of MAS at birth were included in this survey and were evaluated for PPHN using laboratory investigations, including pulse oximetry, ABG, chest X-ray, ECG and 2D color echocardiography.Results: Nineteen neonates showed PPHN, of them 16 had a shunt reversal at PFO level and the rest at PDA level. Most of these newborns were delivered by emergency cesarean section and were unplanned. A majority of neonates of PPHN (84.21%) were diagnosed within 48 h of life and 73.69% had Downey's score more than 6. Neonates of PPHN had mean PH 7.21 ± 0.07, mean PCO2 53.73 ± 6.8, mean PaO2 61.10 ± 10.61 and mean PaO2/FiO2 144.03 ± 46.31.Conclusions: PPHN is a genuine problem in MAS-born neonates and is commonly seen in neonates born by unplanned and unmonitored delivery, and the prevalence of PPHN can be reduced by providing good antenatal care, regular follow up of high-risk pregnancy. 2D echocardiography is an important point of care in the diagnosis of PPHN in nursery and should be promoted in nurseries of developing countries as being engaged in developed countries for more reliable treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine transfusion compatibility of maternal RBCs for her neonate up to 4 weeks of age, irrespective of maternal-neonatal ABO mismatch. Methods: This was a prospective observational study involving eligible mothers with their neonates delivered in participating site from 1 July 2012 till 31 December 2012. Mother's blood was collected before child birth. Neonatal blood sample was collected from placental end, shortly after birth. Blood Groups of mother-baby pair were individually tested for ABO and Rh-D groups. Pairs with negative Rh-D antigen/s or with same ABO blood groups were excluded. Thus, 28 pairs with both maternal and neonatal samples positive for Rh-D antigen and with different maternal neonatal ABO blood groups were included in the study. Blood samples were collected at birth and at 4 weeks. Cross matching was done at birth and at 4 weeks for each pair with standard blood bank protocols. Results: All 28 pairs showed positive compatibility with standard blood bank cross-matching protocols at birth and at 4 weeks. Conclusions: Maternal blood irrespective of ABO compatibility might be a viable and potentially acceptable option for her new born baby in neonatal period. This may be especially important in developing world with limited blood bank resources. [ABSTRACT FROM AUTHOR]

Objective: To measure plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA) and vascular endothelial growth factor (VEGF) levels and VEGF gene polymorphisms in fetal circulation in severe preeclampsia. Methods: Cord vessels of singleton gestations complicated with severe preeclampsia 36 weeks or more (n = 31) and controls were sampled upon delivery for analyte measuring. Additionally, DNA was extracted from umbilical vein whole blood to determine the frequency of VEGF gene single nucleotide polymorphisms (SNPs): −2578 A/C, −1498 C/T, −1154 A/G, −634 C/G and +936 C/T. Coefficient correlations between analyte levels and placental and neonatal weight were calculated. Results: NO plasma levels in umbilical vessels (artery and vein) were significantly higher in preeclampsia cases as compared to controls (4.67 ± 3.0 vs. 0.82 ± 0.90; 4.46 ± 3.0 vs. 0.82 ± 0.99 mmol/L, respectively, p = 0.0001 both). ADMA levels displayed a similar increased trend in both fetal vessels, but this did not reach statistical significance (2.57 ± 1.03 vs. 2.34 ± 0.57; 2.74 ± 0.94 vs. 2.42 ± 0.59 mmol/L, respectively, p > 0.05). VEGF was significantly lower in artery but not in vein in preeclampsia cases (200.48 ± 225.62 vs. 338.61 ± 287.03 pg/mL, p = 0.04). A significant positive correlation was found between NO and ADMA levels (artery and vein) among preeclampsia cases. Overall, the frequency of the studied VEGF gene SNPs did not differ among pre-eclamptic cases and controls; nevertheless, a significant trend toward lower umbilical vein VEGF levels was observed in pre-eclampsia cases in the presence of -2578 CC and −1154 AG genotypes. Conclusion: Near term gestations complicated with severe preeclampsia presented higher NO levels in fetal circulation, which correlated to ADMA and lower artery VEGF values. More research is warranted to confirm that selected VEGF SNPs may be associated with lower umbilical vein VEGF. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension. Methods: 60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL-6, IL-8, TNF-α) were measured. The clinical outcome was also recorded. Results: The findings show that interleukin concentrations (IL-6, IL-8, TNF-α) were significantly decreased between 0 and 72 hours ( p < 0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group. Conclusions: When inhaled, NO was co-administered with concentration of O2 <45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a cellular signaling molecule and a powerful vasodilator. NO modulates basal pulmonary vascular tone and it is important to reduce blood pressure and to treat hypoxemic respiratory failure, such as persistent pulmonary hypertension (PPHN) in newborns. PPHN is defined as a failure of normal pulmonary vascular adaptation at or soon after birth, resulting in a persisting high pulmonary vascular resistance. iNO therapy decreases the need of extracorporeal membrane oxygenation (ECMO) although it did not reduce mortality of these patients. Severe meconial aspiration syndrome is associated with PPHN, resulting in severe hypoxemia; iNO administration combined with HFV results in ameliorate oxygenation. The cause of hypoxemic respiratory failure in patients with congenital diaphragmatic hernia (CDH) is complex. CDH patients experienced oxygenation improvement after iNO therapy, but they can be often considered iNO poor responders. In some cases iNO therapy can reduce the need of ECMO in presurgical stabilization. The pathophysiology of respiratory failure and the potential risks differ substantially in preterm infants. Pulmonary hypertension can complicate respiratory failure in preterm babies. Current evidence does not support use of iNO in early routine, early rescue or layer rescue regimens in the care of preterm infants. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the frequency of persistent pulmonary hypertension of the newborn (PPHN) following elective cesarean at greater than 34 weeks' gestation in an academically affiliated community hospital. Methods. Retrospective cohort study involving chart review of 300 newborns with PPHN between 1999 and 2006. Infants less than 34 weeks' or with congenital anomalies were excluded. Subjects were divided into two groups: (1) intended vaginal delivery and (2) elective cesarean. Results. A total of 125 neonates were included. In all, 46 were delivered vaginally, 53 by cesarean after a trial of labor, and 26 by elective cesarean. No statistically significant differences were noted between groups in birth weight, gestational age, or length of stay. The crude relative risk (RR) of PPHN in cesareans prior to labor (elective cesareans) when compared to intended vaginal deliveries was 2.0 (95%% CI 1.3-3.1). The RR of PPHN in elective cesareans when compared to spontaneous labor resulting in vaginal deliveries was 3.4 (95%% CI 2.1-5.5). The adjusted RRs for these outcomes comparing the same delivery groups when considering gestational age at birth (less vs. equal to or more than 37 weeks') were 2.2 (95%% CI 1.4-3.4) and 3.7 (95%% CI 2.3-6.1), and birth weight (less vs. equal to or more than 2500 g) were 1.9 (95%% 1.3-3.0) and 3.4 (95%% CI 2.1-5.5), respectively. The incidence of PPHN in the elective cesarean group was 6.9 per 1000 deliveries. The number of cesareans to be avoided to prevent one case of PPHN in this cohort was 387 (number needed to harm, 95%% CI 206.8-3003.1). Conclusions. Our findings include a high rate of PPHN following elective cesarean delivery, and suggest that physicians should consider this added morbidity when performing elective cesareans. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition that is characterized by supra-systemic pulmonary vascular resistance causing rightto- left shunting through the ductus arteriosus and/or foramen ovale, leading to a vicious cycle of hypoxemia, acidosis and further pulmonary vasoconstriction. Advances in neonatology including surfactant instillation, high-frequency ventilation, extracorporeal membrane oxygenation and, most importantly, inhaled nitric oxide (INO), have revolutionized the management of PPHN. However, given that INO does not improve oxygenation in a significant proportion (30-40%) of cases, there is an urgent need to consider other therapeutic options for PPHN. The issue is more important for developing nations with a higher PPHN-related health burden and limited resources. This article discusses the evidence about INO in term and preterm neonates in brief, and focuses mainly on the potential alternative drugs in the management of PPHN. [ABSTRACT FROM AUTHOR]

The prominence of cardiovascular diseases has prompted investigations into alternative treatment options, including tissue engineering. Currently, the biggest limitation in cardiac tissue engineering lies in delivering oxygen to all cells within the construct. Synthetic oxygen carriers hold much promise in that they have high affinity for oxygen and can be supplemented to culture medium without adverse effect on the cells. This review highlights two complementary studies by our group that utilized oxygen carriers in cardiac tissue engineering. Experimental and modeling studies were performed to evaluate the effect of a perfluorocarbon (PFC)-based synthetic oxygen carrier, OxygentTM, on oxygen supply within tissue engineered cardiac constructs. Porous biorubber scaffolds with an array of parallel channels mimicking the capillary network were seeded with cardiomyocytes and fibroblasts, and cultivated in medium supplemented with PFC. The presence of PFC enhanced the transport of oxygen, increased oxygen concentrations, and yielded constructs that displayed stronger cardiac-like phenotype. [ABSTRACT FROM AUTHOR]

Objectives. Twin to twin transfusion syndrome (TTTS) is one of the most important problems for perinatal management of monochorionic twins. Since TTTS is deeply related to the prognoses of both fetuses, fetal circulation and placental blood flow of monochorionic twins were studied with the purpose of clarifying characteristic features.Methods. The patterns and numbers of vascular anastomoses were checked on the placental surface, arterio-arterial (A-A) anastomosed vessels by ultrasound, and circulatory changes were studied with relation to uterine contraction.Results. The high risk of monochorionic twin pregnancies was largely related to the patterns of vascular anatomy of the placenta and numbers of anastomosed vessels. The first placental vascular connection detected in vivo was the A-A anastomosis characterized by the bidirectional flow waveform in pulsed Doppler velocimetry.Conclusion. TTTS is related to anastomosed vessels on the surface of placenta. To manage and prevent TTTS, fetal circulation and placental blood flow should be carefully observed. [ABSTRACT FROM AUTHOR]

Smooth muscle cells are relatively rare cells in the microvessels of the normal adult lung but develop in high numbers in the clinical pulmonary hypertensions (PHs). Understanding this cellular response has profound implications for determining the pathogenesis of PH, and for the development of therapeutic strategies, yet little is known of the angiogenic molecules responsible. The authors have previously shown that interstitial fibroblasts, and intermediate cells, are the progenitors of smooth muscle cells developing in adult lung microvessels in an in vivo model of experimental PH. The present study evaluates PDGF-Rβ/PDGF-BB, an important angiogenic signaling pathway, using antibodies linked to protein A-gold (pA-AU) and quantitative high-resolution imaging techniques to detect expression by these cells. Each progenitor cell type in the control lung expressed PDGF-Rβ and PDGF-BB. In the hypertensive lung, PDGF-Rβ was highly expressed by fibroblasts developing as perivascular cells, the mean number of pA-AU labeled antigenic sites per cell profile, and their density (μm -2 ), increasing with time: in intermediate cells the mean number of sites per cell profile, although not their density (μm -2 ), also increased with time but less so than in the fibroblasts. In clear contrast to the RTK, constitutive expression levels of PDGF-BB were low in each progenitor cell type and remained restricted in the hypertensive lung. [ABSTRACT FROM AUTHOR]

Background and objectives: Patent ductus arteriosus (PDA) is a significant cause of morbidity and mortality in preterm infants. This case series was conducted to investigate the usefulness of paracetamol as a first choice for the treatment of PDA in preterm infants. Subjects and methods: Preterm infants were prospectively enrolled. Treatment with oral paracetamol was started at a dose of 15 mg/kg every 6 h for 3 d, with echocardiographic evaluation performed at the end of the treatment and 2 d after the treatment. Serum paracetamol levels were also evaluated for 24 h after the first dose to ensure the absorption and reaching the therapeutic level. Results: A total of six preterm infants were prospectively enrolled. Five infants with PDA were successfully treated with oral paracetamol. Only one patient did not respond to paracetamol treatment whereas another one received a second cure due to reopening of the ductus. Conclusion: Paracetamol may be a useful treatment option for the primer treatment of PDA in preterm infants. If paracetamol is shown to be effective in a large series, because of low risk of side effects, low cost and preparation is available in enteral form, it may be an advantageous alternative at PDA treatment. [ABSTRACT FROM AUTHOR]

Presents the study entitled "The Effect of Increased Sodium in Feed on Pulmonary Hypertension-induced Ascites and Right Ventricular Failure in Broiler Chickens," at the 2004 Spring Meeting of the WPSA UK Branch.