BACKGROUND Therapeutic hypothermia (TH), initiated < 6h of life, is the standard treatment for... more BACKGROUND Therapeutic hypothermia (TH), initiated < 6h of life, is the standard treatment for infants with moderate to severe hypoxic ischemic encephalopathy (HIE). While preclinical studies show that TH is more effective when started early, little clinical data exists. OBJECTIVES The objectives of our study are to examine the effect of early vs. late TH on the severity and pattern of brain injury on MRI and on the neurodevelopmental outcomes. DESIGN/METHODS This retrospective cohort included infants with HIE treated with TH at a level three neonatal intensive care unit between 2009 and 2016. Babies were grouped into: early cooling (TH started ≤ 180 minutes of life) or late cooling (TH started > 180 minutes of life). Two radiologists evaluated the severity and pattern of brain injury on MRI using both NICHD and Barkovich scoring system. Neurodevelopmental outcomes were evaluated at 4, 10, 18 and 48 months. RESULTS Ninety-four patients (median gestational age 39 weeks; median ...
ObjectiveTo examine the influence of timing of initiation of therapeutic hypothermia (TH) on brai... more ObjectiveTo examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months.DesignRetrospective cohort study.SettingTertiary neonatal intensive care unit in Ontario, Canada.PatientsNinety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group.InterventionWhole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH).Main outcome measuresBrain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old.ResultsTH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group ...
American journal of physiology. Lung cellular and molecular physiology, Jan 9, 2018
Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonat... more Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, while having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT. Rat pups were exposed to air or hypoxia (13% O2) from postnatal days 1 to 21. Dose-response prevention studies were conducted from days 1-21 to determine the optimal dose of NaNO2. Animals then received rescue therapy with daily s.c. NaNO2 (20 mg/kg), vehicle or were continuously exposed to iNO (20 ppm) from days 14-21. Chronic PHT secondary to hypoxia was both pre...
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
Peripheral tissue injury is one of the well-described morbidities associated with stays in the ne... more Peripheral tissue injury is one of the well-described morbidities associated with stays in the neonatal intensive care unit. Despite the potential long-term disability associated with this event, the current available therapeutic options remain very limited. Topical nitroglycerin has emerged as a promising agent for the treatment of tissue injury in infants. The present article includes a review of the currently available evidence on the use of topical nitroglycerin in the neonatal population, and describes a unique case involving successful use of 2% nitroglycerin in the late treatment of prolonged tissue ischemia in a newborn infant.
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
BACKGROUND Therapeutic hypothermia (TH), initiated < 6h of life, is the standard treatment for... more BACKGROUND Therapeutic hypothermia (TH), initiated < 6h of life, is the standard treatment for infants with moderate to severe hypoxic ischemic encephalopathy (HIE). While preclinical studies show that TH is more effective when started early, little clinical data exists. OBJECTIVES The objectives of our study are to examine the effect of early vs. late TH on the severity and pattern of brain injury on MRI and on the neurodevelopmental outcomes. DESIGN/METHODS This retrospective cohort included infants with HIE treated with TH at a level three neonatal intensive care unit between 2009 and 2016. Babies were grouped into: early cooling (TH started ≤ 180 minutes of life) or late cooling (TH started > 180 minutes of life). Two radiologists evaluated the severity and pattern of brain injury on MRI using both NICHD and Barkovich scoring system. Neurodevelopmental outcomes were evaluated at 4, 10, 18 and 48 months. RESULTS Ninety-four patients (median gestational age 39 weeks; median ...
ObjectiveTo examine the influence of timing of initiation of therapeutic hypothermia (TH) on brai... more ObjectiveTo examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months.DesignRetrospective cohort study.SettingTertiary neonatal intensive care unit in Ontario, Canada.PatientsNinety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group.InterventionWhole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH).Main outcome measuresBrain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old.ResultsTH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group ...
American journal of physiology. Lung cellular and molecular physiology, Jan 9, 2018
Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonat... more Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, while having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT. Rat pups were exposed to air or hypoxia (13% O2) from postnatal days 1 to 21. Dose-response prevention studies were conducted from days 1-21 to determine the optimal dose of NaNO2. Animals then received rescue therapy with daily s.c. NaNO2 (20 mg/kg), vehicle or were continuously exposed to iNO (20 ppm) from days 14-21. Chronic PHT secondary to hypoxia was both pre...
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
Peripheral tissue injury is one of the well-described morbidities associated with stays in the ne... more Peripheral tissue injury is one of the well-described morbidities associated with stays in the neonatal intensive care unit. Despite the potential long-term disability associated with this event, the current available therapeutic options remain very limited. Topical nitroglycerin has emerged as a promising agent for the treatment of tissue injury in infants. The present article includes a review of the currently available evidence on the use of topical nitroglycerin in the neonatal population, and describes a unique case involving successful use of 2% nitroglycerin in the late treatment of prolonged tissue ischemia in a newborn infant.
American journal of medical genetics. Part A, Jan 21, 2015
We present the investigation and management of a premature, hypotensive neonate born after a preg... more We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most oft...
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Papers by Nadya Fadel