Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including some that are linked to transformation and some that are probably bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent transaminases BCAT1 and BCAT2, likely as a bystander effect, thereby decreasing glutamate levels and increasing dependence on glutaminase for the biosynthesis of glutamate and one of its products, glutathione. Inhibiting glutaminase specifically sensitized IDH mutant glioma cells to oxidative stress in vitro and to radiation in vitro and in vivo. These findings highlight the complementary roles for BCATs and glutaminase in glutamate biosynthesis, explain the sensitivity of IDH mutant cells to glutaminase inhibitors, and suggest a strategy for maximizing the effectiveness of such inhibitors against IDH mutant gliomas.

EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection.

Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.

The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis.

More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 The canonical function of the RB1 gene product, pRB, is to repress the E2F transcription factor family, but pRB also functions to regulate cellular differentiation in part through its binding to the histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that KDM5A promotes SCLC proliferation and SCLC's neuroendocrine differentiation phenotype in part by sustaining expression of the neuroendocrine transcription factor ASCL1. Mechanistically, we found that KDM5A sustains ASCL1 levels and neuroendocrine differentiation by repressing NOTCH2 and NOTCH target genes. To test the role of KDM5A in SCLC tumorigenesis in vivo, we developed a CRISPR/Cas9-based mouse model of SCLC by delivering an adenovirus (or an adeno-associated virus [AAV]) that expresses Cre recombinase and sgRNAs targeting Rb1, Tp53, and Rbl2 into the lungs of Lox-Stop-Lox Cas9 mice. Coinclusion of a KDM5A sgRNA decreased SCLC tumorigenesis and metastasis, and the SCLCs that formed despite the absence of KDM5A had higher NOTCH activity compared to KDM5A+/+ SCLCs. This work establishes a role for KDM5A in SCLC tumorigenesis and suggests that KDM5 inhibitors should be explored as treatments for SCLC.

H3K9 methylation drives resistance to androgen receptor-antagonist therapy in prostate cancer.

Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response that blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation to antiandrogens, which enabled transcriptional silencing of REs that otherwise stimulate interferon signaling and glucocorticoid receptor expression. Elevated expression of terminal H3K9me3 writers was associated with poor patient hormonal therapy outcomes. Forced expression of H3K9me3 writers conferred resistance, whereas inhibiting H3K9-trimethylation writers and readers restored RE expression, blocking antiandrogen resistance. Our work reveals a drug resistance axis that integrates multiple cellular signaling elements and identifies potential pharmacologic vulnerabilities.

Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis.

Nocturnal hypoxaemia, which is common in chronic obstructive pulmonary disease (COPD) patients, is associated with skeletal muscle loss or sarcopenia, which contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of hypoxia in skeletal muscle occurs through the duration of sleep followed by normoxia during the day, in contrast to recurrent brief hypoxic episodes during obstructive sleep apnoea (OSA). Adaptive cellular responses to PIH are not known. Responses to PIH induced by three cycles of 8 h hypoxia followed by 16 h normoxia were compared to those during chronic hypoxia (CH) or normoxia for 72 h in murine C2C12 and human inducible pluripotent stem cell-derived differentiated myotubes. RNA sequencing followed by downstream analyses were complemented by experimental validation of responses that included both unique and shared perturbations in ribosomal and mitochondrial function during PIH and CH. A sarcopenic phenotype characterized by decreased myotube diameter and protein synthesis, and increased phosphorylation of eIF2α (Ser51) by eIF2α kinase, and of GCN-2 (general controlled non-derepressed-2), occurred during both PIH and CH. Mitochondrial oxidative dysfunction, disrupted supercomplex assembly, lower activity of Complexes I, III, IV and V, and reduced intermediary metabolite concentrations occurred during PIH and CH. Decreased mitochondrial fission occurred during CH. Physiological relevance was established in skeletal muscle of mice with COPD that had increased phosphorylation of eIF2α, lower protein synthesis and mitochondrial oxidative dysfunction. Molecular and metabolic responses with PIH suggest an adaptive exhaustion with failure to restore homeostasis during normoxia. KEY POINTS: Sarcopenia or skeletal muscle loss is one of the most frequent complications that contributes to mortality and morbidity in patients with chronic obstructive pulmonary disease (COPD). Unlike chronic hypoxia, prolonged intermittent hypoxia is a frequent, underappreciated and clinically relevant model of hypoxia in patients with COPD. We developed a novel, in vitro myotube model of prolonged intermittent hypoxia with molecular and metabolic perturbations, mitochondrial oxidative dysfunction, and consequent sarcopenic phenotype. In vivo studies in skeletal muscle from a mouse model of COPD shared responses with our myotube model, establishing the pathophysiological relevance of our studies. These data lay the foundation for translational studies in human COPD to target prolonged, nocturnal hypoxaemia to prevent sarcopenia in these patients.

Supergrowth and sub-wavelength object imaging.

We further develop the concept of supergrowth [Quantum Stud.: Math. Found.7, 285 (2020)10.1007/s40509-019-00214-5], a phenomenon complementary to superoscillation, defined as the local amplitude growth rate of a function higher than its largest wavenumber. We identify a canonical oscillatory function's superoscillating and supergrowing regions and find the maximum values of local growth rate and wavenumber. Next, we provide a quantitative comparison of lengths and relevant intensities between the superoscillating and the supergrowing regions of a canonical oscillatory function. Our analysis shows that the supergrowing regions contain intensities that are exponentially larger in terms of the highest local wavenumber compared to the superoscillating regions. Finally, we prescribe methods to reconstruct a sub-wavelength object from the imaging data using both superoscillatory and supergrowing point spread functions. Our investigation provides an experimentally preferable alternative to the superoscillation-based superresolution schemes and is relevant to cutting-edge research in far-field sub-wavelength imaging.

Non-invasive ventilation usage and adherence in children and adults with Duchenne muscular dystrophy: A multicenter analysis.

INTRODUCTION/AIMS: Non-invasive ventilation (NIV) is routinely prescribed to support the respiratory system in Duchenne muscular dystrophy (DMD) patients; however, factors improving NIV usage are unclear. We aimed to identify predictors of NIV adherence in DMD patients. METHODS: This was a multicenter retrospective analysis of DMD patients prescribed NIV and followed at (1) The Hospital for Sick Children, Canada; (2) Rady Children's Hospital San Diego, USA; and (3) University of California San Diego Health, USA, between February 2016 and October 2020. The primary and secondary outcomes were 90-day period NIV adherence and clinical and socioeconomic predictors of NIV adherence. RESULTS: We identified 59 DMD patients prescribed NIV (mean ± SD age = 20.1 ± 6.7 y). Overall, percentage of nights used, and average nightly usage, were 79.9 ± 31.1% and 7.23 ± 4.12 h, respectively. Compared with children, adults had higher percentage of nights used (92.9 ± 16.9% vs. 70.4 ± 36.9%; P < .05), and average nightly usage (9.5 ± 4.7 h vs. 5.3 ± 3.7 h; P < .05). Non-English language (P = .01), and absence of deflazacort prescription (P = .02) were significantly associated with higher percentage of nights used while Hispanic ethnicity (P = .01), low household income (P = .02), and absence of deflazacort prescription (P = .02) were significantly associated with higher nightly usage. Based on univariable analysis, older age and declining forced vital capacity were associated with increased percentage of nights used and increased average nightly usage. DISCUSSION: Certain clinical and socioeconomic determinants had a significant impact on NIV adherence in DMD patients, providing insight into those at risk for high versus low compliance with respiratory therapy.

Long-Term Cardiovascular Outcomes of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Using an Institution Based Algorithm.

Cardiovascular involvement is a major cause of inpatient and intensive care unit morbidity related to Multisystem inflammatory syndrome in children (MIS-C). The objective of this study was to identify long-term cardiovascular manifestations of MIS-C. We included 80 consecutive patients admitted to the intensive care unit with MIS-C who were evaluated for a year in our follow-up clinic using an institution protocol. The outcome measures were cardiac biomarkers (troponin and BNP), electrocardiogram changes, echocardiographic findings cardiovascular magnetic resonance (CMR) and graded-exercise stress test (GXT) findings. The cohort included patients aged between 6 months and 17 years (median 9 years; 48.8% females). At the peak of the disease 81.3% had abnormal BNP and 58.8% had troponin leak which reduced to 33.8% and 18.8% respectively at discharge with complete normalization by 6 weeks post-discharge. At admission 33.8% had systolic dysfunction, which improved to 11.3% at discharge with complete resolution by 2 weeks. Coronary artery abnormalities were seen in 17.5% during the illness with complete resolution by 2 weeks post discharge except one (1.9%) with persistent giant aneurysm at 1 year-follow up. CMR was performed at 6 months in 23 patient and demonstrated 4 patients with persistent late gadolinium enhancement (17.4%). Normal exercise capacity with no ectopy was seen in the 31 qualifying patients that underwent a GXT. There is significant heterogeneity in the cardiovascular manifestations of MIS-C. Although majority of the cardiovascular manifestations resolve within 6 weeks, diastolic dysfunction, CAA and myocardial scar may persist in a small subset of patients warranting a structured long-term follow-up strategy.

Vitmain B12 as Severity and Prognostic Marker in Chronic Liver Disease.

INTRODUCTION: Chronic liver disease is an immuno-compromised state is well known established fact but there are falsely elevated vitamin B12 levels in patients with chronic liver disease, which can be used as severity and prognostic marker. This study was designed to investigate the association between vitamin B12 levels and liver disease severity and long term prognosis in patients with chronic liver disease. MATERIALS: An observational longitudinal study was carried over a period of 6 months among indoor patients admitted in department of medicine of a tertiary care hospital in North-Eastern India. A total of 50 patients diagnosed with chronic liver disease were enrolled. Serum vitamin B12 concentration and other blood parameters were determined. The data were analyzed accordingly by descriptive statistics using Spss for the result. RESULT: The study population were predominantly male with mean age 50.80 ± 10.35. Mean total serum vitamin B12 concentration was significantly higher in patients with chronic liver disease (1639 ± 504 pg/ml) when compared to normal people (650 ± 300pg/ml). Also among patients with chronic liver disease Child-Pugh C (1858 ± 359pg/mL) had higher B12 levels when compared to those with Child-Pugh B (1076 ± 370 pg/mL). Out of 50 people, 4 were died and their mean B12 was (2113 ± 112 pg/ml). CONCLUSION: Falsely increased B12 levels are due to increased excretion of vitamin B12 in to serum from the liver and these serum B12 levels correlates with the severity and prognosis of the patient. References Sugihara T, Koda M, Okamoto T, et al. Falsely elevated serum vitamin B12 levels were associated with the severity and prognosis of chronic viral liver disease. Yonago Acta Med 2017;60(1):31-39. Dou J, Xu W, Ye B, et al. Serum vitamin B12 levels as indicators of disease severity and mortality of patients with acute-on-chronic liver failure. Clin Chim Acta 2012;413(23-24):1809-1812.

Monitoring early-season agricultural drought using temporal Sentinel-1 SAR-based combined drought index.

Early-season agricultural drought is frequent over South Asian region due to delayed or deficient monsoon rainfall. These drought events often cause delay in sowing and can even result in crop failure. The present study focuses on monitoring early-season agricultural drought in a semi-arid region of India over 5-year period (2016-2020). It utilizes hydro-climatic and biophysical variables to develop a combined drought index (CDI), which integrates anomalies in soil moisture conditions, rainfall, and crop-sown area progression. Synthetic aperture radar (SAR)-based soil moisture index (SMI) represents in situ measured soil moisture with reasonable accuracy (r=0.68). Based on the highest F1-score, SAR backscatter in VH (vertical transmit-horizontal receive) polarization with specific values for parameter threshold (-18.63 dB) and slope threshold (-0.072) is selected to determine the start of season (SoS) with a validation accuracy of 73.53%. The CDI approach is used to monitor early-season agricultural drought and identified drought conditions during June-July in 2019 and during July in 2018. Conversely, 2020 experienced consistently wet conditions, while 2016 and 2017 had near-normal conditions. Overall, the study highlights the use of SAR data for early-season agricultural drought monitoring, which is mainly governed by soil moisture-driven crop-sowing progression. The proposed methodology holds potential for effective monitoring, management, and decision-making in early-season agricultural drought scenarios.

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models.

Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2α transcription factor (also known as EPAS1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.

Cardiovascular Magnetic Resonance in Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: Institutional Protocol-Based Medium-Term Follow-up Study.

Multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19 infection in previously healthy children often results in subtle but persistent echocardiographic abnormalities despite complete clinical recovery. This study was done to investigate medium-term cardiovascular outcomes of patients with MIS-C using cardiovascular magnetic resonance imaging (CMR). This is a single-center retrospective study of patients aged less than 21 years, diagnosed with MIS-C who received an outpatient CMR, around 6 months after discharge. CMR was done in patients with significant troponin leak or depressed LVEF. CMR performed on a GE Signa HDxt 1.5 Tesla magnet with a myocarditis protocol. Diagnosis of myocarditis was determined by the original Lake Louise Criteria. There were 21 patients with a median age of 11 years, (IQR 8-13 years), who underwent CMR at median follow-up duration of 6 months (IQR 5-7 months). At the peak of illness during admission, there were 95.2% patients with abnormal Troponin I and BNP. By echocardiogram, 76.2% had left ventricular systolic dysfunction and 9.5% had coronary ectasia, which all resolved by 6 months. By CMR, there were five patients (23.8%) with abnormal left atrial volume, one patient (4.8%) with an abnormal indexed left ventricular end-diastolic volume, and three patients (15%) with abnormal LVEF. There was no evidence of myocardial edema in T2-weighted image sequence. There were three patients with persistent late gadolinium enhancement (14.3%). Follow-up CMR is a useful tool in diagnosing subtle myocardial abnormalities and guide necessity for future follow-up.

Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.

The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate the stability of the HIF transcription factor. We recently showed that loss of EglN2, however, also leads to down-regulation of Cyclin D1 and decreased cell proliferation in a HIF-independent manner. Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3a. FOXO transcription factors can repress Cyclin D1 transcription. Failure to hydroxylate FOXO3a promotes its accumulation in cells, which in turn suppresses Cyclin D1 expression. These findings provide new insights into post-transcriptional control of FOXO3a and provide a new avenue for pharmacologically altering Cyclin D1 activity.

Net ecosystem CO2 exchange from jute crop (Corchorus olitorius L.) and its environmental drivers in tropical Indo-Gangetic plain using open-path eddy covariance technique.

Present study is a maiden attempt to assess net ecosystem exchange (NEE) of carbon dioxide (CO2) flux from jute crop (Corchorus olitorius L.) in the Indo-Gangetic plain by using open-path eddy covariance (EC) technique. Diurnal variations of NEE were strongly influenced by growth stages of jute crop. Daytime peak NEE varied from - 5 µmol m-2 s-1 (in germination stage) to - 23 µmol m-2 s-1 (in fibre development stage). The ecosystem was net CO2 source during nighttime with an average NEE value of 5-8 µmol m-2 s-1. Combining both daytime and nighttime CO2 fluxes, jute ecosystem was found to be a net CO2 sink on a daily basis except the initial 9 days from date of sowing. Seasonal and growth stage-wise NEEs were computed, and the seasonal total NEE over the jute season was found to be - 268.5 gC m-2 (i.e. 10.3 t CO2 ha-1). In different jute growth stages, diurnal variations of NEE were strongly correlated (R2 > 0.9) with photosynthetic photon flux density (PPFD). Ecosystem level photosynthetic efficiency parameters were estimated at each growth stage of jute crop using the Michaelis-Menten equation. The maximum values of photosynthetic capacity (Pmax, 63.3 ± 1.15 µmol CO2 m-2 s-1) and apparent quantum yield (α, 0.072 ± 0.0045 µmol CO2 µmol photon-1) were observed during the active vegetative stage, and the fibre development stage, respectively. Results of the present study would significantly contribute to understanding of the carbon flux from the Indian agro-ecosystems, which otherwise are very sparse.

Coalescing lessons from oxygen sensing, tumor metabolism, and epigenetics to target VHL loss in kidney cancer.

Inactivation of the von Hippel Lindau tumor suppressor protein (pVHL) is a hallmark of clear cell Renal Cell Carcinoma (ccRCC), which is the most common form of kidney cancer in adults. In complex with Elongin B/C, pVHL functions as the substrate recognition subunit of a ubiquitin ligase, perhaps best known to target the hypoxia inducible factor (HIF) transcription factor for ubiquitin-dependent proteolysis. Beyond kidney cancer, the pseudo-hypoxic state caused due to chronic HIF activation in pVHL-deficient cells has become a biological model to study hypoxia's profound effects on tumor angiogenesis, metabolism, and epigenetics. However, a number of HIF-independent substrates of pVHL, which function in a broad range of biological pathways, have also been discovered. Independently, the development of high-throughput chemical and genetic screening strategies have enabled the identification of novel, HIF-independent, targetable dependencies in ccRCC. In this review we summarize the history of pVHL and HIF mediated oxygen sensing, discuss the current status of this field, and identify critical challenges that need to be overcome. The confluence of historical discovery, development of unbiased screening strategies, and the evolution of medicinal chemistry has allowed us to begin therapeutically targeting vulnerabilities that emerge due to pVHL loss in ccRCC. Ongoing mechanistic studies on the biological consequences of pVHL loss, therefore, are likely to become the cornerstones of modern therapeutics in renal cancer.

Assessing lodging damage of jute crop due to super cyclone Amphan using multi-temporal Sentinel-1 and Sentinel-2 data over parts of West Bengal, India.

The present study is a maiden attempt to assess jute crop lodging due to super cyclone Amphan (20 May 2020) by synergistic use of Sentinel-2 (optical) and Sentinel-1 (SAR) data over part of West Bengal, India. Pre-event Sentinel-2 data (9 April, 14 May) along with the ground information were used to map the jute crop of the affected districts with accuracy of 85%. The cross-polarized backscatter (σ0VH) of Sentinel-1 was found to be sensitive to the sudden change in the canopy structure due to lodging and partial flooding. [Formula: see text](σ0VH_22 May - σ0VH_16 May) indicating post-event damage was > 2.5 dB over the affected jute crop and [Formula: see text] (σ0VH_22 May - σ0VH_28 May) representing post-event recovery showed > 1.5 dB for recovered crop, depending on the crop vigor/height. Decision matrix was prepared combining [Formula: see text] and [Formula: see text] for NDVI-based crop vigor strata (low, medium, and high) to classify the area into affected, marginally affected and normal. Overall accuracy of the classified map was found to be 84.12% with kappa coefficient of 0.74. Nearly, 12.5% of the jute area, i.e., 38,119 ha was found to be either affected or marginally affected due to Amphan and distributed in the southern part of Murshidabad, north-eastern Nadia, northern 24 Paraganas (N), and middle region of Hooghli district. Geospatial map of block-wise affected jute area was prepared to facilitate informed decision making. The study demonstrated an operational methodology for assessing crop lodging due to natural calamities to support relief management and crop insurance.

Transcatheter Intervention for Treatment of Coronary Stenosis After Unroofing of the Anomalous Left Coronary Artery.

Anomalous origin of left coronary artery (LCA) from the right coronary cusp with an intramural course is usually managed with unroofing of the intramural segment. Available literature demonstrates an uneventful course following surgery in most patients. Coronary stenosis following the unroofing procedure treated with percutaneous coronary intervention has not been described in the past. We describe a case where an 11-year-old girl with anomalous origin of the LCA from the right coronary cusp presented with near syncope. Surgical unroofing of the intramural segment was done without any post-operative complications and the patient remained asymptomatic for 9 months. She then presented with chest pain, abnormal troponin levels, and ST-T wave changes on EKG. A CT angiogram done revealed short segment narrowing of the LCA near its origin. Cardiac catheterization with coronary angiography demonstrated short segment narrowing of the LCA just distal to origin. Stenting of the left main coronary artery was done with a drug eluting stent. She underwent the procedure without complications. The patient continued to be asymptomatic 16 months after placement of the stent and there was no residual stenosis seen on a repeat CT angiogram at 3 months after the procedure.

Emerging trends in the prenatal diagnosis of complex CHD and its influence on infant mortality in this cohort.

BACKGROUND: Fetal echocardiography is the main modality of prenatal diagnosis of CHD. This study was done to describe the trends and benefits associated with prenatal diagnosis of complex CHD at a tertiary care centre. METHODS: Retrospective chart review of patients with complex CHD over an 18-year period was performed. Rates of prenatal detection along with early and late infant mortality outcomes were studied. RESULTS: Of 381 complex CHD patients born during the study period, 68.8% were diagnosed prenatally. Prenatal detection rate increased during the study period from low-50s in the first quarter to mid-80s in the last quarter (p=0.001). Rate of detection of conotruncal anomalies increased over the study period. No infant mortality benefit was noted with prenatal detection. CONCLUSIONS: Improved obstetrical screening indications and techniques have contributed to higher proportions of prenatal diagnosis of complex CHD. However, prenatal diagnosis did not confer survival benefits in infancy in our study.

Impact of prenatal diagnosis of complex congenital heart disease on neonatal and infant morbidity and mortality.

OBJECTIVES: The objective of this study was to analyze the benefits associated with prenatal diagnosis of complex congenital heart disease (CHD) on preoperative morbidity, 30-day and 1-year mortality in this population. METHOD: This was a retrospective review of patients with complex CHD born at our tertiary care center over a 10-year period. Date analysis using Student t test and chi-square test. RESULTS: The overall rate of prenatal detection of complex CHD was 68.1%. A steady increase in the number of complex CHD diagnosed prenatally was noted during the study period. The prenatal diagnosis of complex CHD was associated with significant reduction in the incidence of the following preoperative parameters: antibiotic use, mechanical ventilation, inotropic support, hepatic and renal dysfunction, and acidosis. These beneficial effects were more significant in ductal-dependent cardiac anomalies. However, there were no neonatal and infant survival benefits in association with prenatal diagnosis. CONCLUSION: Prenatal diagnosis of complex CHD leads to improved preoperative morbidity, especially in patients with ductal-dependent cardiac anomalies. No survival benefits were noted with prenatal diagnosis of complex CHD.