Histopathologic features of alveolar capillary dysplasia with misalignment of pulmonary veins with atypical clinical presentation.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare neonatal lung disease with fatal outcome. Typically, respiratory symptoms present in the first 24 hours of life and patients die within the neonatal period. Atypical, delayed clinical presentations and/or longer survival have also been reported. Here, we studied the clinicopathologic relationship of ACD/MPV by examining 16 cases of ACD/MPV, focusing on atypical features. Based on the presence of diffuse vs. focal/patchy ACD/MPV histopathologic changes, we divided the cases into classic and nonclassic pathology groups. MPV was found in all ACD/MPV. Ten of 16 cases exhibited classic diffuse abnormalities, while 6 of 16 had a nonclassic focal/patchy distribution. However, among 7 patients with atypical clinical features, only 2 had nonclassic pathology, while 4 out of 9 clinically typical cases had nonclassic ACD/MPV pathology. Marked intrapulmonary aberrant arteriovenous vessels were present in all atypical cases. In conclusion, clinical presentation is not always correlated with histopathology in ACD/MPV. Atypical ACD/MPV should be suspected in any infants with fulminant pulmonary hypertension. Abnormal pulmonary veins and aberrant intraseptal vessels are the most important clues for diagnosis. Additional studies are needed for further elucidation of diagnostic histological criteria of atypical ACD/MPV and to explore its pathogenesis.

Extra-Corporeal Membrane Oxygenation for Neonatal Respiratory Support.

To review our experience with Extra-Corporeal Membrane Oxygenation (ECMO) for respiratory support in neonates. From 1989 to 2018 2114 patients underwent respiratory ECMO support, with 764 (36%) neonates. Veno-Venous (V-V) cannulation was used in 428 (56%) neonates and Veno-Arterial (V-A) in 336 (44%). Historically V-V ECMO was our preferred modality, but due to lack of suitable cannula in the last 7 years V-A was used in 209/228 (92%) neonates. Mean and inter-quartile range of ECMO duration was 117 hours (inter-quartile range 90 to 164 hours). Overall 724 (95%) neonates survived to ECMO decannulation, with 640 (84%) hospital discharge. Survival varied with underlying diagnosis: meconium aspiration 98% (354/362), persistent pulmonary hypertension 80% (120/151), congenital diaphragmatic hernia 66% (82/124), sepsis 59% (35/59), pneumonia 86% (6/7), other 71% (43/61). Survival was 86% with V-V and 80% with V-A cannulation, better than ELSO Registry with 77% V-V and 63% V-A. Major complications: cerebral infarction/hemorrhage in 4.7% (31.1% survival to discharge), renal replacement therapy in 17.6% (58.1% survival to discharge), new infection in 2.9%, with negative impact on survival (30%). Following a circuit design modification and subsequent reduction in heparin requirement, intracerebral hemorrhage decreased to 9/299 (3.0%) radiologically proven cerebral infarction/hemorrhage. We concluded (1) outcomes from neonatal ECMO in our large case series were excellent, with better survival and lower complication rate than reported in ELSO registry. (2) These results highlight the benefits of ECMO service in high volume units. (3) The similar survival rate seen in neonates with V-A and V-V cannulation differs from the ELSO register; this may reflect the change in cannulation enforced by lack of suitable V-V cannula and all neonates undergoing V-A cannulation.

An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment and outcome.

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.

Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life.

OBJECTIVE: To assess postdischarge mortality and morbidity in infants diagnosed with different etiologies and severities of persistent pulmonary hypertension of the newborn (PPHN), and to identify risk factors for these adverse clinical outcomes. STUDY DESIGN: This was a population-based study using an administrative dataset linking birth and death certificates, hospital discharge and readmissions records from 2005 to 2012 in California. Cases were infants ≥34 weeks' gestational age with International Classification of Diseases,9th edition, codes consistent with PPHN. The primary outcome was defined as postdischarge mortality or hospital readmission during the first year of life. Crude and adjusted risk ratio (aRR) with 95% CIs were calculated to quantify the risk for the primary outcome and to identify risk factors. RESULTS: Infants with PPHN (n = 7847) had an aRR of 3.5 (95% CI, 3.3-3.7) for the primary outcome compared with infants without PPHN (n = 3 974 536), and infants with only mild PPHN (n = 2477) had an aRR of 2.2 (95% CI, 2.0-2.5). Infants with congenital diaphragmatic hernia as the etiology for PPHN had an aRR of 8.2 (95% CI, 6.7-10.2) and infants with meconium aspiration syndrome had an aRR of 4.2 (95% CI, 3.7-4.6) compared with infants without PPHN. Hispanic ethnicity, small for gestational age, severe PPHN, and etiology of PPHN were risk factors for the primary outcome. CONCLUSIONS: The postdischarge morbidity burden of infants with PPHN is large. These findings extend to infants with mild PPHN and etiologies with pulmonary vascular changes that are thought to be short term and recoverable. These data could inform counseling of parents.

Factors and Outcomes of Persistent Pulmonary Hypertension of the Newborn Associated with Acute Kidney Injury in Thai Neonates.

OBJECTIVE: This study aims to determine the risk factors and outcome of persistent pulmonary hypertension of the newborn (PPHN)-associated acute kidney injury (AKI). STUDY DESIGN: Infants diagnosed with PPHN at Hat Yai Hospital from January 2012 to December 2016 were retrospectively reviewed. RESULTS: Of the 109 included PPHN infants, 28.4% (31/109) died, and AKI was found in 28.4% following neonatal KDIGO classification. Of the 31, 19 who died (61.3%) reached stage 1, 3 (9.7%) reached stage 2, and 9 (29.0%) reached stage 3. AKI (all stages combined) was significantly associated with increased mortality with an odds ratio (OR) of 8.71 (95% confidence interval [CI], 3.37-22.49). Multivariate logistic regression analysis indicated that male gender (adjusted OR = 8.56; 95% CI = 0.84-85.09) and urine output of < 1 mL/kg/h in 12 hours of admission (adjusted OR = 15.57; 95% CI = 2.58-93.98) were the main factors associated with an increased risk for AKI, while birth by cesarean delivery was associated with reduced risk of AKI (adjusted OR = 0.10; 95% CI = 0.16-0.68). CONCLUSION: The incidence of AKI in PPHN was high in this study, and this complication was also significantly associated with higher mortality. In PPHN neonates, AKI should be especially closely monitored in males and infants who have a urine output of < 1 mL/kg/h in the first 12 hours of admission.

Persistent Pulmonary Hypertension of the Newborn in Late Preterm and Term Infants in California.

BACKGROUND AND OBJECTIVES: There are limited epidemiologic data on persistent pulmonary hypertension of the newborn (PPHN). We sought to describe the incidence and 1-year mortality of PPHN by its underlying cause, and to identify risk factors for PPHN in a contemporary population-based dataset. METHODS: The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharges, readmissions, and birth and death certificates from 1 year before to 1 year after birth. We searched the database (2007-2011) for cases of PPHN (identified by International Classification of Diseases, Ninth Revision codes), including infants ≥34 weeks' gestational age without congenital heart disease. Multivariate Poisson regression was used to identify risk factors associated with PPHN; results are presented as risk ratios, 95% confidence intervals. RESULTS: Incidence of PPHN was 0.18% (3277 cases/1 781 156 live births). Infection was the most common cause (30.0%). One-year mortality was 7.6%; infants with congenital anomalies of the respiratory tract had the highest mortality (32.0%). Risk factors independently associated with PPHN included gestational age <37 weeks, black race, large and small for gestational age, maternal preexisting and gestational diabetes, obesity, and advanced age. Female sex, Hispanic ethnicity, and multiple gestation were protective against PPHN. CONCLUSIONS: This risk factor profile will aid clinicians identifying infants at increased risk for PPHN, as they are at greater risk for rapid clinical deterioration.

Oral Sildenafil Use In Neonates With Persistent Pulmonary Hypertension Of Newborn.

BACKGROUND: The prevalence of PPHN has been estimated at 1.9 per 1000 live births. After the discovery of iNO's, its efficacy and benefit in PPHN is well established. Even in the best of centers equipped with iNo and ECMO the mortality is around 20%. Also, iNO is expensive and difficult to administer and monitor which makes it difficult choice in our part of the world. Furthermore About 40% of patients do not respond or have rebound pulmonary hypertension after discontinuation. Owing to these reasons, other treatment modalities like phosphodiesterase inhibitors such as Sildenafil need to be evaluated. METHODS: We report a retrospective case series of eighteen patients with PPHN admitted in NICU and treated with oral sildenafil. RESULTS: Three (17%) babies had mild, 5 (28%) moderate and 10 (55%) severe PPHN based on echocardiography. Sildenafil was started on all patients on a mean of 1.67 days and stopped on mean 12.6 days. Initial fio2 was 100%, which after starting sildenafil decreased gradually to 40% on mean 10 days. Average length of stay in NICU was 13 days. Twelve (67%) patients survived whereas 6 (33%) expired (Figure 2). No improvement in oxygen Index after 36 hours (p<0.05) was the independent predicting risk factor for PPHN related mortality in the expired patients. CONCLUSIONS: Oral sildenafil can be a used in conjunction with other treatment modalities for PPHN especially in resource limited settings. However further studies regarding its comparative efficacy need to be done.

Management of pulmonary hypertension in infants with congenital diaphragmatic hernia.

In infants with congenital diaphragmatic hernia (CDH), a posterolateral diaphragmatic defect results in herniation of abdominal contents into the chest and compression of the intrathoracic structures. In the most severe cases, hypoplasia of the ipsilateral and contralateral lungs, severe pulmonary hypertension (PH) and left ventricular (LV) hypoplasia/dysfunction all contribute to increased mortality. The management of PH in CDH is complicated by structural and functional changes in the heart, pulmonary vasculature, airways and lung parenchyma; consequently, determining optimal management strategies is challenging. Treatment of PH in patients with CDH changes as the underlying pathophysiology evolves in the days and weeks after birth. During the early transition, the use of pulmonary vasodilators is limited by LV structural and functional abnormalities, and pulmonary vasodilators such as inhaled nitric oxide (iNO) may have a limited role (for example, stabilization for extracorporeal membrane oxygenation (ECMO), treatment of marked preductal desaturation and treatment of PH as LV performance improves). In contrast, subacute treatment of PH in CDH with iNO has an important role in recurrent or persistent PH and potentially improves survival. Chronic PH and vascular abnormalities may persist into childhood in patients with CDH, contributing to late mortality. It is unclear how pulmonary vasodilator therapies, such as iNO, sildenafil and bosentan, will modulate late outcomes in CDH with late/chronic PH.

Persistent Pulmonary Hypertension of the Newborn with D-transposition of the Great Arteries: Management and Prognosis.

OBJECTIVE: There is a paucity of data on clinical correlates and outcomes of pulmonary hypertension (PH) in patients with D-transposition of the great arteries (D-TGA) in the era of inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Our objective was to compare clinical characteristics and outcomes of infants with D-TGA with and without PH, defined as hypoxemia that required iNO and/or ECMO. METHODS: We undertook a single-center retrospective chart review involving infants with gestational age ≥32 weeks with D-TGA who, underwent arterial switch operation over a 12-year period. Demographic and clinical data, details of the repair and postoperative complications were abstracted. RESULTS: Our cohort (n = 93), 61 (66%) of whom were males, had a mean (SD) gestational age and birth weight of 38.7 (1.8) weeks and 3.2 (0.6) kg, respectively. PH requiring iNO and/or ECMO was noted in 20 (21.5%) infants. Infants with PH had significantly lower birth weight [2.8 (0.56) vs. 3.33 (0.61)] and gestational age [37.7 (2.1) vs. 38.9 (1.7)] than those without PH. Rates of postoperative complications (duration of pressors, sedative medicaiton and duration of hospital stay, and mechanical ventilation were higher in the group with PH. Of the five (5.4%) infants who died, four received iNO and ECMO. Death or postoperative complications tended to be associated with lower gestational age [OR 0.689; 95% CI: 0.469-1.012, P = 0.058] but not with D-TGA category or bypass duration. CONCLUSIONS: Despite aggressive treatment with iNO and ECMO, the coexistence of PH in this population is associated with higher rates of mortality and postoperative complications. Our results also suggest that an early term birth may be associated with PH in infants with D-TGA.

Acute kidney injury and pneumothorax are risk factors for mortality in persistent pulmonary hypertension of the newborn in Thai neonates.

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.

Nitric therapy in preterm infants: rationalised approach based on functional neonatal echocardiography.

AIM: Use of inhaled nitric oxide (iNO) in preterm infants is not supported by current evidence. In 2013, in Australia and New Zealand, 14% infants' ≤25 weeks of gestations were administered iNO. Within the cohort administered iNO, we aimed to identify subgroups where it may be more efficacious and compared characteristics before and after the set-up of the functional echocardiography (fEcho) programme. METHODS: A retrospective audit for the period 2000-2013 involving preterm infants administered iNO in the first four weeks of life was performed. Comparisons were made between the two time epochs: up to 2007 and post-2007. RESULTS: Eighty-five infants fulfilled the inclusion criteria; 62 (73%) were ≤28 weeks of gestation; 51 (60%) survived. Amongst survivors, gestation and birthweight were higher and oxygenation index (OI) was lower. Fourteen (16.5%) infants weighed small for gestation age; survival was lower in this subgroup (6/14, 43%, p = 0.0005). The fEcho programme increased prenitric assessments for a definitive diagnosis and monitoring; iNO was started earlier, at a lower OI with a trend towards reduced usage (hours). CONCLUSION: Characteristics of subgroups (within the cohort of infants ≤34 weeks of gestation) more likely to benefit from iNO therapy were identified. Use of fEcho could rationalise usage.

Right ventricular echocardiographic indices predict poor outcomes in infants with persistent pulmonary hypertension of the newborn.

AIMS: Infants with persistent pulmonary hypertension of the newborn (PPHN) have elevated pulmonary vascular resistance that can lead to right ventricular (RV) failure and death. Clinicians must decide which infants will fail conventional therapy and require transfer to extra corporeal membrane oxygenation (ECMO) centres, but accurate echocardiographic predictors have not been identified. We assessed echocardiographic measurements of RV pressure and function in predicting progression to death or ECMO in infants with PPHN. METHODS AND RESULTS: Echocardiograms for infants ≥35-week gestation with a clinical diagnosis of PPHN were retrospectively reviewed. Traditional and strain echocardiographic measures were compared for those with or without the primary outcome of ECMO/cardiovascular death. Receiver operator curves identified cut points for measures that were significantly different. Of the 86 subjects analysed, 25 (29%) of the patients had the primary outcome of ECMO/death. The ECMO/death group had diminished tricuspid annular plane systolic excursion (TAPSE; P = 0.002) and RV global longitudinal peak strain (GLPS; P = 0.03), a predominant right-to-left shunt across the patent ductus arteriosus (PDA; P = 0.05), and an elevated oxygenation index (OI; P < 0.001). Sensitivity/specificity for TAPSE <4 mm was 56 and 85%, and for GLPS greater than or equal to -9% was 52 and 77%. CONCLUSION: TAPSE, GLPS, and right-to-left PDA shunting were associated with progression to death/ECMO. RV free wall strain was not associated with the outcome, suggesting that diminished global strain better reflects clinical outcomes in this group. These thresholds may assist in the decision-making to transfer high-risk infants to ECMO centres.

Experience with the Avalon® bicaval double-lumen veno-venous cannula for neonatal respiratory ECMO.

OBJECTIVE: We report a single centre experience of neonatal respiratory ECMO using the Avalon® double-lumen venous cannula and compare it with reports in the literature. RESULTS: Between 2008 and 2012, the Avalon® cannula was used in 72 neonates: median age at cannulation was 1.8 days (IQR 1.2-2.8 days) and bodyweight 3.4 Kg (3.0-3.7 Kg). Meconium aspiration syndrome (61.1%), persistent hypertension of the newborn (25%) and congenital diaphragmatic hernia (5.6%) were the most common diagnoses. Complications occurred in 19 patients (26.4%): cannula site bleeding in 6 (8.3%), the cannula perforating the right atrial wall and requiring emergency midline sternotomy in 5 (6.9%) and the cannula needing repositioning in 3 (4.2%). Overall survival at discharge or transfer to the referring hospital was 88.8%. Successful wean off ECMO occurred in 68 patients (94.4%) after a median of 90.5 hours (63.4-136.11). ECMO support was withdrawn in 4 patients (5.6%). CONCLUSIONS: The Avalon® dual-lumen veno-venous cannula can be used for respiratory ECMO in the neonatal population. However, as the incidence of right atrial perforation is not negligible, we suspended its used in this group of patients.

Preferential streaming of the ductus venosus toward the right atrium is associated with a worse outcome despite a higher rate of invasive procedures in human fetuses with left diaphragmatic hernia.

PURPOSE: Preferential streaming of the ductus venosus (DV) toward the right atrium has been observed in fetuses with left diaphragmatic hernia (LDH). The purpose of this retrospective study was to compare survival rates to discharge between a group with preferential streaming of the DV toward the right heart and a group in which this abnormal flow pattern was not present. MATERIALS AND METHODS: We retrospectively searched our patient records for fetuses with LDH in whom liver position, DV streaming and postnatal outcome information was available. 55 cases were found and divided into two groups: Group I fetuses exhibited abnormal DV streaming toward the right side of the heart; group II fetuses did not. Various prognostic and outcome parameters were compared. RESULTS: 62 % of group I fetuses and 88 % of group II fetuses survived to discharge (p = 0.032). Fetoscopic tracheal balloon occlusion (FETO) was performed in 66 % of group I fetuses and 23 % of group II fetuses (p = 0.003). Postnatal ECMO therapy was performed in 55 % of group I fetuses and 23 % of group II infants (p = 0.025). Moderate to severe chronic lung disease in survivors was observed in 56 % of the survivors of group I and 9 % of the survivors of group II (p = 0.002). CONCLUSION: Preferential streaming of the DV toward the right heart in human fetuses with left-sided diaphragmatic hernia was associated with a poorer postnatal outcome despite a higher rate of invasive pre- and postnatal procedures compared to fetuses without this flow abnormality. Specifically, abnormal DV streaming was found to be an independent predictor for FETO.

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience.

PURPOSE: Despite improvements in the management of persistent pulmonary hypertension of the newborn (PPHN), a number of infants with inadequate gas exchange are treated with extracorporeal membrane oxygenation (ECMO). The objectives of this study were to use the Extracorporeal Life Support Organization Registry to review the outcomes of neonates with PPHN receiving ECMO, and to identify pre-ECMO variables that may be associated with increased mortality. MATERIALS AND METHODS: The study is a retrospective analysis of all patients with PPHN supported with ECMO and reported to the Extracorporeal Life Support Organization registry from 2000 to 2010. Prematurity was defined as <37 wk gestation. Univariate analysis was performed using Student's t-test or Fisher's exact test. Variables found to be statistically significant underwent multivariate analysis by logistic regression. Kaplan-Meier survival curves were generated to analyze the relationship between duration of ECMO support and patient survival. RESULTS: A total of 1569 neonates with PPHN received ECMO support during the study period, at an average age of 3.1 d of life and for a duration of 6.9 d. Survival among neonates with PPHN receiving ECMO support was 81%, and those receiving support for 7, 10, 14, and 21 d survived at rates of 88%, 78%, 55%, and 25%, respectively. By logistic regression, prematurity (P < 0.01), pre-ECMO pH ≤7.2 (P = 0.02), pre-ECMO SaO(2) ≤65% (P = 0.01), and duration of ECMO ≥7 d (P < 0.001) were independent predictors of death in this group. An average of 2.2 complications occurred per patient, with cardiovascular, mechanical, and renal complications being the most common. CONCLUSIONS: Neonates with PPHN have high survival rates with ECMO support. Prematurity, acidosis, and profound hypoxemia are independently associated with increased mortality. Furthermore, prolonged ECMO support (>7 d) is associated with a higher risk of mortality in this cohort than in patients supported for <1 wk.

Persistent pulmonary hypertension of the newborn in twin-twin transfusion syndrome following fetoscopic laser surgery.

OBJECTIVE: We investigated persistent pulmonary hypertension of the newborn (PPHN) among monochorionic-diamniotic (MD) twins. METHODS: A retrospective cohort study examined MD twins from 195 deliveries and 373 live-born neonates at our center. RESULTS: PPHN occurred in three cases (3/373: 0.8%), all of which were recipients of twin-twin transfusion syndrome (TTTS), after fetoscopic laser surgery (FLS) (3/117: 2.6%). Although the clinical course of the three cases differed, all cardiothoracic area ratios exceeded 40%, and other cardiac parameters also worsened after FLS. CONCLUSIONS: The occurrence of PPHN in TTTS recipients should be noted, particularly when fetal cardiac function declines following FLS.

A right-to-left or bidirectional ductal shunt in preterm neonates: grave implication?

We delineate the natural history of a right-to-left or bidirectional (RL/BD) patent ductus arteriosus (PDA) in preterm infants and compare outcomes of an RL/BD and a left-to-right (LR) ductal shunt. We performed a retrospective chart review of preterm infants (< 32 weeks), who, between 2 and 30 days of age, had an RL/BD PDA > 1.5 mm (study group; N = 74) or an LR PDA (N = 87) on echocardiogram (ECHO). In the study group, 27% of infants who were of significantly lower gestational age and birth weight had a "prolonged" RL/BD PDA on two or more ECHOs. Infants with RL/BD PDA required significantly greater surfactant (98.6% versus 94.2%) and less PDA therapy (27% versus 92%) and had higher mortality (48.6% versus 21.8%) compared with those with LR PDA. On regression analysis, lower gestation (odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.15 to 1.83) and RL/BD PDA (OR 4.74; 95% CI: 2.18 to 10.3) were significantly associated with mortality. The independent association between an RL/BD PDA shunt and mortality warrants further investigation. Insights into the etiology of pulmonary hypertension may optimize outcomes in this population.

Predicting mortality in infants with persistent pulmonary hypertension of the newborn with the Score for Neonatal Acute Physiology-Version II (SNAP-II) in Thai neonates.

AIM: To evaluate the ability of the Score for Neonatal Acute Physiology-Version II (SNAP-II) to predict mortality in infants with persistent pulmonary hypertension of the newborn (PPHN). METHODS: A prospective cohort study of 41 infants with PPHN admitted to our neonatal intensive care unit between June 2008 and March 2010, who underwent a SNAP-II test within 12 h of admission. RESULTS: Of the 41 infants, 14 died (34.1%) and 27 survived (65.9%). The SNAP-II scores were significantly higher in infants who died (50.1 ± 18.5 vs. 35.7 ± 16.8, P=0.02). Each point increase in the SNAP score increased the odds of mortality by 1.04 [95% confidence interval (CI) 1.01-1.07, P<0.01]. Infants who had a SNAP-II score of ≥ 43 had the greatest mortality risk with an odds ratio (OR) of 10.00 (95% CI 1.03-97.50). The SNAP-II model showed moderate discrimination in predicting mortality with a result of 0.72 (95% CI 0.56-0.88) under the receiver operating characteristic curve. The lowest blood pressure, lowest PaO(2)/FIO(2) ratio, and urine output within the first 12 h of admission were also independently found to be good predictors of an increased risk for death. CONCLUSION: The SNAP-II scoring system significantly predicted mortality. PPHN infants with a SNAP-II score of ≥ 43 had the greatest mortality risk.

Bedside lung mechanics predict survival in hypoplastic lung disease.

Newer bedside pulmonary mechanics using conventional ventilators allow for CONTINUOUS serial determinations of tidal volume (V(T)). We sought to determine whether the degree of pulmonary hypoplasia could be measured using bedside pulmonary graphics and whether survival could be predicted in potential extracorporeal membrane oxygenation (ECMO) candidates. Data on all neonates considered for or treated with ECMO at our center between April 2000 and March 2005 were collected. The "maximal bedside V(T)" was measured daily at the peak pressure where "beaking" began with a peak end expiratory pressure of 4 cm H(2)O. Twenty-two patients were reviewed: eight ECMO plus fourteen similar patients in whom the threshold for ECMO intervention was not achieved. Independent of need for ECMO, any patient with V(T) of < 3 mL/kg or < 0.2 mL/cm length died ( N = 4). All other measures of lung capacity or blood gas assessments were less valuable than V(T) in predicting survival. We conclude that bedside V(T) can be easily measured and that values < 3 mL/kg or < 0.2 mL/cm length demarcate severe lung hypoplasia, which in our patient population was incompatible with survival. We speculate that bedside V(T) may assist in evaluating the utility of ECMO.