Children with Hirschsprung's disease have high morbidity in the first 5 years of life.

BACKGROUND: Hirschsprung's disease is a rare congenital anomaly of the colon with absence of the ganglionic nerve cells. The treatment of the anomaly is surgical. METHODS: This population-based data-linkage cohort study was part of the EUROlinkCAT project and investigated mortality and morbidity for the first 5 years of life for European children diagnosed with Hirschsprung's disease. Nine population-based registries in five countries from the European surveillance of congenital anomalies network (EUROCAT) participated. Data on children born 1995-2014 and diagnosed with Hirschsprung's disease were linked to hospital databases. All analyses were adjusted for region and length of follow-up, which differed by registry. RESULTS: The study included 680 children with Hirschsprung's disease. One-year survival was 97.7% (95% CI: 96.4-98.7). Overall, 85% (82-87) had a code for a specified intestinal surgery within the first year increasing to 92% (90-94) before age 5 years. The median age at the first intestinal surgery up to 5 years was 28 days (11-46) and the median number of intestinal surgical procedures was 3.5 (3.1-3.9). Thirty days mortality after neonatal surgery (within 28 days after birth) was 0.9% (0.2-2.5) for children with a code for intestinal surgery within the first 28 days after birth and there were no deaths for children with a code for stoma surgery in the neonatal period. CONCLUSION: Children with Hirschsprung's disease have a high morbidity in the first 5 years of life requiring more surgical procedures in addition to the initial surgery. Mortality after neonatal surgery is low.

Impact of COVID-19 restrictions on self-poisoning behaviour with mild analgesics in Danish youth.

BACKGROUND: The COVID-19 pandemic prompted the implementation of precautions to contain the disease, including lockdowns and social isolation. Previous studies have investigated suicide rates among children and adolescents during the pandemic and have found varying results. We speculated how the two lockdowns influenced suicidal behaviour in children and adolescents in Denmark. OBJECTIVE: This study aimed to investigate the effect of lockdowns during the COVID-19 pandemic on suicide attempts, as measured by the incidence rate in all self-poisonings with mild analgesics among children and adolescents. METHODS: This national Danish registry-based study on children and adolescents used Poisson regression and interrupted time series analysis to examine the incidence rates and trends of self-poisonings with mild analgesics from 2019 to mid-2021. RESULTS: For the period of this study, 1655 self-poisonings were registered. During the first lockdown, there was a slight, not statistically significant, decrease in self-poisoning rates (incidence rate ratio [IRR]) 0.98) compared to no lockdown. During the second lockdown, there was a significant increase in self-poisonings for the whole Danish population (IRR 1.85) with girls being slightly higher at risk (IRR 1.87). Being a girl or between the ages of 13-17 years old were risk factors for self-poisoning. CONCLUSION: These findings indicate that the restrictions enforced during the second lockdown greatly impacted youth mental health, especially girls, leading to an 85% increase in self-poisonings. We hope for increased awareness of mental health in children and adolescents during possible future lockdowns.

Higher risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury and child abuse in children with congenital anomalies: Data from the EUROlinkCAT study.

AIM: The aim is to examine the risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury/poisoning and child abuse in children with and without a congenital anomaly up to age 5 and 10 years. METHODS: This is a population-based data linkage cohort study linking information from the European Surveillance of Congenital Anomalies network (EUROCAT) and birth registries to hospital discharge databases. We included 91 504 live born children with major congenital anomalies born from 1995 to 2014 from nine EUROCAT registries in five countries and 1 960 727 live born children without congenital anomalies (reference children). Prevalence and relative risk (RR) were estimated for each of the co-morbidities using Kaplan-Meier survival estimates. RESULTS: Children with congenital anomalies had higher risks of the co-morbidities than reference children. The prevalences in the reference children were generally very low. The RR was 13.8 (95% CI 12.5-15.1) for cerebral palsy, 2.5 (95% CI 2.4-2.6) for seizures/epilepsy, 40.8 (95% CI 33.2-50.2) for visual impairments, 10.0 (95% CI 9.2-10.9) for hearing loss, 3.6 (95% CI 3.2-4.2) for cancer, 1.5 (95% CI 1.4-1.5) for injuries/poisoning and 2.4 (95% CI 1.7-3.4) for child abuse. CONCLUSION: Children with congenital anomalies were more likely to be diagnosed with the specified co-morbidities compared to reference children.

Hospital care in the first 10 years of life of children with congenital anomalies in six European countries: data from the EUROlinkCAT cohort linkage study.

OBJECTIVE: To quantify the hospital care for children born with a major congenital anomaly up to 10 years of age compared with children without a congenital anomaly. DESIGN, SETTING AND PATIENTS: 79 591 children with congenital anomalies and 2 021 772 children without congenital anomalies born 1995-2014 in six European countries in seven regions covered by congenital anomaly registries were linked to inpatient electronic health records up to their 10th birthday. MAIN OUTCOME MEASURES: Number of days in hospital and number of surgeries. RESULTS: During the first year of life among the seven regions, a median of 2.4% (IQR: 2.3, 3.2) of children with a congenital anomaly accounted for 18% (14, 24) of days in hospital and 63% (62, 76) of surgeries. Over the first 10 years of life, the percentages were 17% (15, 20) of days in hospital and 20% (19, 22) of surgeries. Children with congenital anomalies spent 8.8 (7.5, 9.9) times longer in hospital during their first year of life than children without anomalies (18 days compared with 2 days) and 5 (4.1-6.1) times longer aged, 5-9 (0.5 vs 0.1 days). In the first year of life, children with gastrointestinal anomalies spent 40 times longer and those with severe heart anomalies 20 times longer in hospital reducing to over 5 times longer when aged 5-9. CONCLUSIONS: Children with a congenital anomaly consume a significant proportion of hospital care resources. Priority should be given to public health primary prevention measures to reduce the risk of congenital anomalies.

Transesophageal echocardiography of cardiac function in Nile crocodiles - A novel tool for assessing complex hemodynamic patterns.

BACKGROUND: The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and pressures. Crocodiles have retained two aortic arches; one from each ventricle, that communicate via Foramen of Panizza, immediately distally from the aortic valves. Moreover, crocodiles can regulate vascular resistance in the pulmonary portion of the right ventricular outflow tract (RVOT). These unique features allow for a complex regulation of shunting between the pulmonary and systemic circulations. Studies on crocodile shunting have predominantly been based on invasive measurements, but here we report on the use of echocardiography. METHODS: Experiments were performed on seven pentobarbital anaesthetized juvenile Nile crocodiles (length and mass of 192 ± 13 cm and 26 ± 5 kg, respectively). Echocardiographic imaging was performed using a transesophageal (TEE) approach. All images were EKG-gated. RESULTS: We obtain excellent views of cardiac structures and central vasculature through the esophagus. Standard imaging planes were defined for both long- and short axis views of the left ventricle and truncus arteriosus. For the RV, only a short axis view could be obtained. Color Doppler was used to visualize flow. Pulsed waved Doppler for measuring flow profiles across the atrioventricular valves, in the two RVOTs and the left ventricular outflow tract. Shunting across the Foramen of Panizza could be visualized and gated to the EKG. CONCLUSION: TEE can be used to image the unique features of the crocodile heart and allow for in-vivo imaging of the complex shunting hemodynamics, including timing of cardiac shunts.

Timing of Cardiac Surgical Interventions and Postoperative Mortality in Children With Severe Congenital Heart Defects Across Europe: Data From the EUROlinkCAT Study.

BACKGROUND: The purpose of this study was to evaluate the timing of the first cardiac surgery, the number of cardiac surgeries performed, and 30-day postoperative mortality rate for children with severe congenital heart defects (sCHDs) in their first 5 years of life. METHODS AND RESULTS: This was a population-based data linkage cohort study linking information from 9 European congenital anomaly registries to vital statistics and hospital databases. Data were extracted for 5693 children with sCHDs born from 1995 to 2004. Subgroup analyses were performed for specific types of sCHD. Children with sCHDs underwent their first surgical intervention at a median age of 3.6 (95% CI, 2.6-4.5) weeks. The timing of the first surgery for most subtypes of sCHD was consistent across Europe. In the first 5 years of life, children with hypoplastic left heart underwent the most cardiac surgeries, with a median of 4.4 (95% CI, 3.1-5.6). The 30-day postoperative mortality rate in children aged <1 year ranged from 1.1% (95% CI, 0.5%-2.1%) for tetralogy of Fallot to 23% (95% CI, 12%-37%) for Ebstein anomaly. The 30-day postoperative mortality rate was highest for children undergoing surgery in the first month of life. Overall 5-year survival for sCHD was <90% for all sCHDs, except transposition of the great arteries, tetralogy of Fallot, and coarctation of the aorta. CONCLUSIONS: There were no major differences among the 9 regions in the timing, 30-day postoperative mortality rate, and number of operations performed for sCHD. Despite an overall good prognosis for most congenital heart defects, some lesions were still associated with substantial postoperative death.

Special Challenges in PET Imaging of Ectothermic Vertebrates.

The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.

Oral-only antibiotics for bone and joint infections in children: study protocol for a nationwide randomised open-label non-inferiority trial.

INTRODUCTION: Children with bone and joint infections are traditionally treated with intravenous antibiotics for 3-10 days, followed by oral antibiotics. Oral-only treatment has not been tested in randomised trials. METHODS AND ANALYSIS: Children (3 months to 18 years) will be randomised 1:1 with the experimental group receiving high-dose oral antibiotics and the control group receiving intravenous antibiotics with a shift in both groups to standard oral antibiotics after clinical and paraclinical improvement. Children in need of acute surgery or systemic features requiring intravenous therapy, including septic shock, are excluded. The primary outcome is defined as a normal blinded standardised clinical assessment 6 months after end of treatment. Secondary outcomes are non-acute treatment failure and recurrent infection. Outcomes will be compared by a non-inferiority assumption with an inferiority margin of 5%. ETHICS AND DISSEMINATION: The trial has the potential to reduce unnecessary hospitalisation and use of intravenous antibiotics in children with bone or joint infections. Due to the close follow-up, exclusion of severely ill children and predefined criteria for discontinuation of the allocated therapy, we expect the risk of treatment failure to be minimal. TRIAL REGISTRATION NUMBER: NCT04563325.

Impact of COVID-19 Restrictions on Acute Gastroenteritis in Children: A Regional, Danish, Register-Based Study.

This study aimed to evaluate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) restrictions such as social distancing on the occurrence of acute gastroenteritis (AGE) among children. This study is a register-based study, including every child seen in the departments of paediatrics with the initial diagnosis of AGE in three neighbouring hospitals in Denmark, from March 2018 through February 2021. The study also included every positive stool sample for AGE-causing pathogens analysed in these three hospitals from children during the same period. The Wilcoxon rank-sum test was used to determine differences between the period during the SARS-CoV-2 restrictions and before. In all, 222,157 children were seen in the three paediatric departments during this period. Of these, 3917 children were diagnosed with AGE. We found a decrease of 46.6% in AGE-related visits per month after the SARS-CoV-2 restrictions were introduced compared to before (p-value < 0.001). Positive stool samples decreased by 38.2% (p-value = 0.008) during the restrictions. This study found that cases of paediatric AGE decreased significantly the during COVID-19 restrictions, suggesting that studies should be conducted to determine whether this reduction was a result of good hand hygiene and social distancing or just a result of altered health-seeking behaviour among children.

Hospital Length of Stay and Surgery among European Children with Rare Structural Congenital Anomalies-A Population-Based Data Linkage Study.

Little is known about morbidity for children with rare structural congenital anomalies. This European, population-based data-linkage cohort study analysed data on hospitalisations and surgical procedures for 5948 children born 1995-2014 with 18 rare structural congenital anomalies from nine EUROCAT registries in five countries. In the first year of life, the median length of stay (LOS) ranged from 3.5 days (anotia) to 53.8 days (atresia of bile ducts). Generally, children with gastrointestinal anomalies, bladder anomalies and Prune-Belly had the longest LOS. At ages 1-4, the median LOS per year was ≤3 days for most anomalies. The proportion of children having surgery before age 5 years ranged from 40% to 100%. The median number of surgical procedures for those under 5 years was two or more for 14 of the 18 anomalies and the highest for children with Prune-Belly at 7.4 (95% CI 2.5-12.3). The median age at first surgery for children with atresia of bile ducts was 8.4 weeks (95% CI 7.6-9.2) which is older than international recommendations. Results from the subset of registries with data up to 10 years of age showed that the need for hospitalisations and surgery continued. The burden of disease in early childhood is high for children with rare structural congenital anomalies.

European study showed that children with congenital anomalies often underwent multiple surgical procedures at different ages across Europe.

AIM: Children with congenital anomalies often require surgery but data on the burden of surgery for these children are limited. METHODS: A population-based record-linkage study in Finland, Wales and regions of Denmark, England, Italy and Spain. A total of 91 504 children with congenital anomalies born in 1995-2014 were followed to their tenth birthday or the end of 2015. Electronic linkage to hospital databases provided data on inpatient surgical procedures and meta-analyses of surgical procedures were performed by age groups. RESULTS: The percentage of children having surgery in the first year was 38% with some differences across regions and 14% also underwent surgery at age 1-4 years. Regional differences in age at the time of their first surgical procedure were observed for children with cleft palate, hydronephrosis, hypospadias, clubfoot and craniosynostosis. The children had a median of 2.0 (95% CI 1.98, 2.02) surgical procedures before age 5 years with children with oesophageal atresia having the highest median number of procedures (4.5; 95% CI 3.3, 5.8). CONCLUSION: A third of children with congenital anomalies required surgery during infancy and often more than one procedure was needed before age 5 years. There was no European consensus on the preferred age for surgery for some anomalies.

Preterm birth and prescriptions for cardiovascular, antiseizure, antibiotics and antiasthmatic medication in children up to 10 years of age: a population-based data linkage cohort study across six European regions.

OBJECTIVES: Preterm children are exposed to many medications in neonatal intensive care units, but little is known about the effect of prematurity on medication use throughout infancy and childhood. We examined prescriptions of cardiovascular medication (CVM), antiseizure medication (ASM), antiasthmatic medication and antibiotics issued/dispensed in the first 10 years of life for very and moderately preterm children compared with term. DESIGN: Population-based data linkage cohort study linking information from birth records to prescription records. SETTING: Six registries from five countries in the EUROlinkCAT study. PARTICIPANTS: The study population included 1 722 912 children, of whom 10 820 (0.6%) were very preterm (<32 weeks gestational age (GA)), 92 814 (5.4%) were moderately preterm (32-36 weeks GA), 1 606 643 (93.3%) were born at term (≥37 weeks GA) and 0.7% had missing GA. Children with major or minor congenital anomalies were excluded (including patent ductus arteriosus). MAIN OUTCOME MEASURES: Relative risk (RR) of receiving a prescription for CVM, ASM, antiasthmatic and antibiotics. RESULTS: Very preterm children had a higher RR of receiving a prescription for CVM and ASM than preterm children. For all preterm children, the RR of having a CVM prescription was 3.58 (95% CI 2.06 to 6.23); 2.06 (95% CI 1.73 to 2.41) for ASM; 1.13 (95% CI 0.99 to 1.29) for antiasthmatics and 0.96 (95% CI 0.93 to 0.99) for antibiotics in the first year of life. Increased prescription of CVM, ASM and antiasthmatics persisted for all 10 years of follow-up. Although the RR was highest for CVM and ASM, in absolute numbers more children received prescriptions for antibiotics (42.34%, 95% CI 38.81% to 45.91%) and antiasthmatics (28.40%, 95% CI 16.07% to 42.649%) than for CVM (0.18%, 95% CI 0.12% to 0.25%) and ASM (0.16%, 95% CI 0.13% to 0.20%) in the first year of life. CONCLUSION: Preterm children had a higher risk of being prescribed/dispensed CVM, ASM and antiasthmatics up to age 10. This study highlights a need for further research into morbidity beyond age 10.

Prescription of cardiovascular medication in children with congenital heart defects across six European Regions from 2000 to 2014: data from the EUROlinkCAT population-based cohort study.

OBJECTIVES: Advances in surgical management strategies have substantially reduced fatality from congenital heart defects (CHD). Decreased infant mortality might be expected, consequentially to result in greater morbidity in older children due to complications later in childhood and adolescence. This study aims to evaluate the use of cardiovascular medication (CVM) as an indicator of disease burden in children born with CHD in the first 10 years of life. DESIGN: Population-based cohort study. SETTING: Six population-based registries from the European Surveillance of Congenital Anomalies (EUROCAT) network participated. Data from live born children with major congenital anomalies (CA) born from 2000 to 2014 were linked to prescription databases. Four groups of children were analysed: CA, CHD, severe CHD (sCHD) and ventricular septal defect (VSD) without sCHD. Live born children without CA were included as reference group. PARTICIPANTS: We obtained data on 61 038 children born with a CA, including 19 678 with CHD, 3392 with sCHD, 12 728 children with VSD without sCHD, and 1 725 496 reference children. RESULTS: Children born with sCHD were the most likely to receive a CVM prescription (42.9%, 95% CI, 26.3 to 58.5) in the first year of life compared with 13.3% (6.7 to 22.0) of children with any CHD, 5.9% (3.7 to 8.7) of children with any CA and 0.1% (0.0 to 0.1) of reference children. Medication was less likely to be prescribed after the first year of life for sCHD; 18.8% (14.8 to 23.1) for children 1-4 years and 15.8% (12.0 to 20.1) 5-9 years. Children with sCHD were most likely to receive a diuretic (36.4%, 18.6 to 54.5), an antihypertensive (6.9%, 3.7 to 11.3) or a beta-blocker (5.5%, 2.9 to9.2). CONCLUSION: Almost half of all children with sCHD were prescribed CVM in their first year of life. For all four groups of children with anomalies, the proportion of children with a CVM prescription decreased with age.

Live birth prevalence of atrioventricular septal defect after the implementation of new prenatal screening guidelines.

INTRODUCTION: In 2004, the Danish Health Authority implemented a new guideline on prenatal screening, offering all pregnant women in Denmark a foetal diagnostic ultrasound scan in the first and second trimester of their pregnancy. One of the diagnoses that may be diagnosed prenatally is congenital heart defect including atrioventricular septal defect (AVSD). AVSD is often associated with Down syndrome (DS). After a prenatal diagnosis of AVSD, parents are offered counselling on the impact of the diagnosis on their child's life. The aim of this study was to describe the impact of changes in prenatal screening programmes on the live birth prevalence of AVSD on the island of Funen, Denmark. METHODS: This was a registry-based descriptive analysis drawing on data from the EUROCAT Registry of Congenital Malformations for Funen County, Denmark. Cases of AVSD and DS from 1990 to 2018 were included. RESULTS: Out of 153,757 births, 60 cases of AVSD were registered, with a total prevalence at 3.9 per 10,000 births. Among all cases, 40% had an associated chromosomal diagnosis. The prenatal detection rate increased by 83% after implementation of the new screening programme. This was paralleled by an increase in the number of cases of termination of pregnancy following foetal anomaly (TOPFA) from 3% to 21% (p-value less-than 0.05) and a 21% reduction in live births among infants with AVSD. CONCLUSIONS: A significant increase in the rate of TOPFA was found, with no difference in the distribution of chromosomal or non-chromosomal status, leading to a 21% reduction in liveborn infants with AVSD. FUNDING: none. TRIAL REGISTRATION: none.

Trends in Antiarrhythmic Drug Use in Denmark Over 19 Years.

Antiarrhythmic drugs are widely used in the treatment of supraventricular and ventricular arrhythmias. Yet, nationwide long-term utilization trends remain unexplored. We examined 19-year trends in the use of antiarrhythmic drugs in Denmark. Using nationwide prescription data, we obtained information on hospital and primary healthcare use of Class I-V antiarrhythmic drugs from 1999 to 2017. Data was stratified according to sex and age groups. From 1999 to 2017, the total use of antiarrhythmic drugs per 1000 inhabitants/day increased 16% from 36.3 in 1999 to 41.9 in 2017 with peak consumption in 2008 (46.5). In primary healthcare, Class I usage decreased from 0.8 to 0.5 defined daily doses (DDD) per 1000 inhabitants/day, driven by a decreased prescription rate of propafenone (0.4 to 0.1) whereas prescription of flecainide (Class Ic) increased from 0.3 to 0.4 DDD per 1000 inhabitants/day (mainly in men of age 45 to 79 years). Class II usage increased from 15.4 to 33.6 DDD per 1000 inhabitants/day. Class III usage decreased from 2.6 to 1.1 DDD per 1000 inhabitants/day, reflecting reduced prescription rate of sotalol (2.1 to 0.2) whereas amiodarone increased from 0.5 to 0.9 (mainly due to increased prescription among men and women >80 years). Class IV usage declined from 8.6 to 2.8 DDD per 1000 inhabitants/day. Finally, Class V drugs decreased 8.1 to 3.3 DDD per 1000 inhabitants/day. In conclusion, during the past 2 decades considerable changes in prescription rate of antiarrhythmic drugs have occurred, most notably a reduction in sotalol and increased usage of flecainide, Class II drugs, and amiodarone.

A novel NAA10 p.(R83H) variant with impaired acetyltransferase activity identified in two boys with ID and microcephaly.

BACKGROUND: N-terminal acetylation is a common protein modification in human cells and is catalysed by N-terminal acetyltransferases (NATs), mostly cotranslationally. The NAA10-NAA15 (NatA) protein complex is the major NAT, responsible for acetylating ~ 40% of human proteins. Recently, NAA10 germline variants were found in patients with the X-linked lethal Ogden syndrome, and in other familial or de novo cases with variable degrees of developmental delay, intellectual disability (ID) and cardiac anomalies. METHODS: Here we report a novel NAA10 (NM_003491.3) c.248G > A, p.(R83H) missense variant in NAA10 which was detected by whole exome sequencing in two unrelated boys with intellectual disability, developmental delay, ADHD like behaviour, very limited speech and cardiac abnormalities. We employ in vitro acetylation assays to functionally test the impact of this variant on NAA10 enzyme activity. RESULTS: Functional characterization of NAA10-R83H by in vitro acetylation assays revealed a reduced enzymatic activity of monomeric NAA10-R83H. This variant is modelled to have an altered charge density in the acetyl-coenzyme A (Ac-CoA) binding region of NAA10. CONCLUSIONS: We show that NAA10-R83H has a reduced monomeric catalytic activity, likely due to impaired enzyme-Ac-CoA binding. Our data support a model where reduced NAA10 and/or NatA activity cause the phenotypes observed in the two patients.

The exaggerated natriuresis of essential hypertension occurs independently of changes in renal medullary blood flow.

AIMS: In patients with essential hypertension, abnormal renal sodium handling includes exaggerated natriuresis in response to extracellular volume expansion. We tested the hypothesis that exaggerated natriuresis is associated with increases in medullary and/or cortical renal blood flow. METHODS: Patients with mild essential hypertension, but no signs of end organ damage, and control subjects were studied after 4 days of dietary standardization (<60 mmol Na+  day-1 ) preceded in patients by a 14-day drug washout period. On the study day, subjects received a 4-hour intravenous volume expansion with saline (2.1% of body mass). Renal medullary and cortical blood flows were measured by PET scanning using H215 O as tracer; anatomical regions of interest were defined by contrast-enhanced CT scanning. RESULTS: In patients, arterial blood pressure increased during volume expansion (107 ± 2-114 ± 3 mm Hg, P < 0.05) in contrast to the control group (92 ± 2-92 ± 2 mm Hg). Renal sodium excretion increased more in patients than in controls (+133 ± 31 µmol min-1 vs +61 ± 14 µmol min-1 , respectively, P < 0.05) confirming exaggerated natriuresis. During volume expansion, renal medullary blood flow did not change significantly in patients (2.8 ± 0.4-2.5 ± 0.5 mL (g tissue)-1  min-1 ) or in controls (3.2 ± 0.3-3.1 ± 0.2 mL (g tissue)-1 min-1 ). In control subjects, renal cortical blood flow fell during volume expansion (4.1 ± 0.3-3.7 ± 0.2 mL (g tissue)-1  min-1 , P < 0.05) in contrast to patients in which deviations remained insignificant. CONCLUSION: Exaggerated natriuresis, a hallmark of essential hypertension, is not mediated by increases in regional, renal blood flow.