Neonatal blood pressure by birth weight, gestational age, and postnatal age: a systematic review.

BACKGROUND: Blood pressure is a vital hemodynamic marker during the neonatal period. However, normative values are often derived from small observational studies. Understanding the normative range would help to identify ideal thresholds for intervention to treat hypotension or hypertension. Therefore, the aim of this study was to assess observed blood pressure values in neonates who have not received any blood-pressure modifying treatments from birth to three months postnatal age and whether these vary according to birth weight, gestational age and postnatal age. METHODS: This was a systematic review. A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on blood pressure in neonates from birth to 3 months of age (PROSPERO ID CRD42018092886). Unpublished data were included where appropriate. RESULTS: Of 3,587 non-duplicate publications identified, 30 were included (one unpublished study). Twelve studies contained data grouped by birth weight, while 23 contained data grouped by gestational age. Study and clinical heterogeneity precluded meta-analyses thus results are presented by subgroup. A consistent blood pressure rise was associated with increasing birth weight, gestational age, and postnatal age. In addition, blood pressure seemed to rise more rapidly in the most preterm and low birth weight neonates. CONCLUSION: Despite blood pressure increasing with birth weight, gestational age, and postnatal age, there was marked blood pressure variability observed throughout. To better define hypotension and hypertension, future studies should develop consistent approaches for factors related to blood pressure variability, including the method and timing of measurement as well as statistical control of relevant patient characteristics.

Risk of Target Organ Damage in Children With Primary Ambulatory Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. METHODS: A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. RESULTS: Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69-8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m2.7; [95% CI, 3.78-6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20-0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02-0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. CONCLUSIONS: Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020189359.

Neonatal hypertension: concerns within and beyond the neonatal intensive care unit.

Neonatal hypertension occurs in 1%-2% of neonates in the neonatal intensive care unit (NICU) although may be underdiagnosed. Blood pressure values in premature neonates change rapidly in the first days and weeks of life which may make it more difficult to recognize abnormal blood pressure values. In addition, the proper blood pressure measurement technique must be used to ensure the accuracy of the measured values as most blood pressure devices are not manufactured specifically for this population. In premature neonates, the cause of the hypertension is most commonly related to prematurity-associated complications or management while in term neonates is more likely to be due to an underlying condition. Both oral and intravenous antihypertensive medications can be used in neonates to treat high blood pressure although none are approved for use in this population by regulatory agencies. The natural history of most neonatal hypertension is that it resolves over the first year or two of life. Of concern are the various neonatal risk factors for later cardiovascular and kidney disease that are present in most NICU graduates. Prematurity increases the risk of adulthood hypertension while intrauterine growth restriction may even lead to hypertension during childhood. From neonates through to adulthood NICU graduates, this review will cover each of these topics in more detail and highlight the aspects of blood pressure management that are established while also highlighting where knowledge gaps exist.

Antenatal and perinatal factors influencing neonatal blood pressure: a systematic review.

OBJECTIVE: A comprehensive understanding of the factors contributing to perinatal blood pressure is vital to ensure optimal postnatal hemodynamic support. The objective of this study was to review existing literature on maternal and perinatal factors influencing blood pressure in neonates up to 3 months corrected age. METHODS: A systematic search of published literature in OVID Medline, OVID Embase and the COCHRANE library identified publications relating to maternal factors affecting blood pressure of neonates up to corrected age of 3 months. Summary data were extracted and compared (PROSPERO CRD42018092886). RESULTS: Of the 3683 non-duplicate publications identified, 44 were eligible for inclusion in this review. Topics elicited were sociodemographic factors, maternal health status, medications, smoking during pregnancy, and cord management at birth. Limited data were available for each factor. Results regarding the impact of these factors on neonatal blood pressure were inconsistent across studies. CONCLUSIONS: There is insufficient evidence to draw definitive conclusions regarding the impact of various maternal and perinatal factors on neonatal blood pressure. Future investigations of neonatal cardiovascular therapies should account for these factors in their study design. Similarly, studies on maternal diseases and perinatal interventions should include neonatal blood pressure as part of their primary or secondary analyses.

Mean Arterial Pressure and Chronic Kidney Disease Progression in the CKiD Cohort.

[Figure: see text].

Determinants of Blood Pressure in Neonates and Infants: Predictable Variability.

The blood pressure (BP) of neonates, especially those born premature, changes rapidly over the first days and weeks of life. Neonatal BPs may be affected by maternal factors, perinatal factors or events, and intrinsic or extrinsic infant factors. Unfortunately, the effect of many maternal health and disease states has only been studied in small numbers or has shown conflicting results. Many events around the time of delivery have the potential to influence the neonatal BP, and while definitive studies are often lacking, some observational data support physiological expectations. The strongest determinants of neonatal BP are the infant factors of gestational age at birth, birth weight, and postmenstrual age. Understanding the expected pattern of BP changes, identifying the potential influencing factors, and accurately measuring the BP are all essential to determine whether there is a BP abnormality present but are also more complex in the neonatal population. This review describes the evidence for maternal conditions, perinatal events, and infant factors to affect neonatal BP. It also explains what is currently known about the changing BP patterns in neonates including those born preterm. In addition, by examining the physiological process of hemodynamic adaptation to the extrauterine environment and compensatory cardiovascular responses, we can gain insight into the expected and unexpected vascular responses, making the variability of neonatal BP seem a little more predictable.

Evidence Gaps in the Identification and Treatment of Hypertension in Children.

The ultimate goal of recognizing and treating hypertension in childhood is to prevent target-organ damage during childhood and to reduce the risk of adulthood cardiovascular disease. The quality of evidence to guide blood pressure management in children is lower than in adult medicine, yet some common findings support clinical practice recommendations. Oscillometric devices are increasingly replacing manual blood pressure measurements, but evidence shows that readings are not equivalent between the 2 methods. In addition, multiple blood pressure readings are needed before diagnosing a child with hypertension, but the optimal number and timing are still being determined. The recent American Academy of Pediatrics blood pressure guideline has revised the normative data tables and included threshold blood pressure limits which seem to identify children with higher cardiovascular risks. Threshold limits vary between guidelines, and the most accurate threshold has yet to be determined. Lifestyle modifications are a cornerstone of hypertension management, but the optimal diet and physical activity changes for beneficial effect are not known. When pharmacotherapy is needed, physicians have used drugs from all antihypertensive classes in children, yet only a few classes have been systematically studied. The long-term cardiovascular consequences of elevated blood pressure during childhood are under investigation and it seems that the lower the childhood blood pressure the better and that the rate of change during childhood is predictive of adulthood disease. With much still to learn, this article summarizes the evidence and the evidence gaps for the diagnosis, investigation, management, and outcomes of pediatric hypertension.

Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis.

OBJECTIVES: To determine the recommended blood pressure (BP) measurement methods in neonates after systematically analyzing the literature regarding proper BP cuff size and measurement location and method. STUDY DESIGN: A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on BP in neonates <3 months of age (PROSPERO ID CRD42018092886). Study data were extracted and analyzed with separate analysis of Bland-Altman studies comparing measurement methods. RESULTS: Of 3587 nonduplicate publications identified, 34 were appropriate for inclusion in the analysis. Four studies evaluating BP cuff size support a recommendation for a cuff width to arm circumference ratio of approximately 0.5. Studies investigating measurement location identified the upper arm as the most accurate and least variable location for oscillometric BP measurement. Analysis of studies using Bland-Altman methods for comparison of intra-arterial to oscillometric BP measurement show that the 2 methods correlate best for mean arterial pressure, whereas systolic BP by the oscillometric method tends to overestimate intra-arterial systolic BP. Compared with intra-arterial methods, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise, especially in neonates with a mean arterial pressure <30 mm Hg. CONCLUSIONS: Proper BP measurement is critical in neonates with naturally lower BP and attention to BP cuff size, location, and method of measurement are essential. With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

Ambulatory blood pressure and carotid intima media thickness in children with type 1 diabetes.

BACKGROUND/OBJECTIVE: Blood pressure abnormalities may play an important role in macrovascular damage in type 1 diabetes. Little is known about blood pressure abnormalities and macrovascular damage in children with type 1 diabetes. METHODS: Children with type 1 diabetes (n = 57) for a short (3 months-2 years; n = 24) or long duration (≥5 years; n = 33) and a group of control children without diabetes (n = 29) completed 24-h ambulatory blood pressure monitoring (ABPM). Carotid intima media thickness (cIMT), a subclinical indicator of atherosclerosis, was assessed by carotid ultrasound. RESULTS: ABPM abnormalities were more prevalent (57% vs 24%, respectively), and daytime, nighttime and 24-h systolic, diastolic, and mean arterial blood pressure indices were higher in children with type 1 diabetes compared to control children. The odds estimate of an ABPM abnormality was 6.68 (95% confidence interval: 1.95, 22.9; P = .003) in children with type 1 diabetes compared to controls after adjusting for age, sex, and BMI standardized for age and sex (zBMI). An interaction between ABPM and zBMI on cIMT was observed. In children with type 1 diabetes and ABPM abnormalities, every 1 SD increase in zBMI was associated with a 0.030 mm increase in cIMT (95% confidence interval: 0.002, 0.041; P = .031). This was not observed in control children with ABPM abnormalities or in children with normal ABPM, regardless of type 1 diabetes status. CONCLUSIONS: Children with type 1 diabetes have a high prevalence of ABPM abnormalities independent of disease duration and this is related to early indicators of cardiovascular damage.

Factors influencing the timing of initiation of renal replacement therapy and choice of modality in children with end-stage kidney disease.

BACKGROUND: Decision-making in pediatric end-stage renal disease (ESRD) is a complex process for patients, families, and physicians. We evaluated the factors influencing the timing of initiation of renal replacement therapy (RRT) and choice of modality in children with ESRD. METHODS: We retrospectively reviewed the RRT decision-making process for all children up to 19 years of age with ESRD, who underwent RRT over an 11-year period (2004 to 2014), at a Canadian pediatric tertiary care center. RRT modalities included peritoneal dialysis (PD), hemodialysis (HD), pre-emptive kidney transplant (PKT), and continuous renal replacement therapy (CRRT). RESULTS: Ninety-two patients progressed to ESRD. RRT was started electively for 58 patients, and urgently for 34 patients. For elective patients, modalities included PD (34%), HD (19%), and PKT (47%). The glomerular filtration rate at initiation of RRT was higher in patients who underwent PKT as opposed to dialysis (11.7 vs. 9.1 ml/min/1.73m2). Medical and quality of life factors, including fatigue and poor concentration, influenced the timing of initiation of elective RRT. Medical factors were primarily important in urgent RRT, including oligoanuria and metabolic disturbances. Medical factors, patient/family preference, and contextual factors such as location of residence influenced choice of modality. CONCLUSIONS: Our study found that the decision-making process in ESRD is multifactorial and involves not only medical factors, but also assessment of social factors, quality of life, and patient/family preference. Bettering our understanding of this decision-making process will positively impact patients and families through more informed decision-making.

Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients.

Background Females with Turner syndrome (TS) carry an elevated risk of aortic dissection. The objective of the study was to assess the biophysical properties of the aorta and ambulatory blood pressure (BP) in females with TS and compare these findings to those in healthy female age-matched controls. Methods This was a prospective cohort study including subjects aged 8-25 years. Utilizing two-dimensional (2D) echocardiography and Doppler, proximal aortic dimensions were measured and biophysical properties of the aorta were calculated including pulse wave velocity (PWV), arterial pressure-strain elastic modulus and stiffness index. Resting BP was measured and ambulatory blood pressure monitoring (ABPM) was performed. Results Of 23 TS patients and 46 controls (median age 16.3 years), aortic annulus, sinus of Valsalva and sinotubular (ST) junction diameters, as well as left ventricular (LV) mass, were significantly greater in TS patients compared with controls when scaled for height2.7, but not for body surface area (BSA), although ascending aorta diameter was greater when scaled for both. Median PWV was faster in TS patients compared to controls (451 vs. 360 cm/s) while arterial pressure-strain elastic modulus and stiffness index were similar. Resting BP was abnormal in seven out of 22 patients and ABPM was abnormal in 16 out of 21 patients. Conclusions Young patients with TS had dilated proximal aortas when scaled for height2.7 and stiffer aortas when compared with healthy female age-matched controls. Moreover, resting BP underdiagnosed pre-hypertension and hypertension compared to ABPM. These findings are consistent with the presence of a primary aortopathy in TS.

Diagnosis, Evaluation, and Management of High Blood Pressure in Children and Adolescents.

Systemic hypertension is a major cause of morbidity and mortality in adulthood. High blood pressure (HBP) and repeated measures of HBP, hypertension (HTN), begin in youth. Knowledge of how best to diagnose, manage, and treat systemic HTN in children and adolescents is important for primary and subspecialty care providers. OBJECTIVES: To provide a technical summary of the methodology used to generate the 2017 "Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents," an update to the 2004 "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents." DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, and Excerpta Medica Database references published between January 2003 and July 2015 followed by an additional search between August 2015 and July 2016. STUDY SELECTION: English-language observational studies and randomized trials. METHODS: Key action statements (KASs) and additional recommendations regarding the diagnosis, management, and treatment of HBP in youth were the product of a detailed systematic review of the literature. A content outline establishing the breadth and depth was followed by the generation of 4 patient, intervention, comparison, outcome, time questions. Key questions addressed: (1) diagnosis of systemic HTN, (2) recommended work-up of systemic HTN, (3) optimal blood pressure (BP) goals, and (4) impact of high BP on indirect markers of cardiovascular disease in youth. Once selected, references were subjected to a 2-person review of the abstract and title followed by a separate 2-person full-text review. Full citation information, population data, findings, benefits and harms of the findings, as well as other key reference information were archived. Selected primary references were then used for KAS generation. Level of evidence (LOE) scoring was assigned for each reference and then in aggregate. Appropriate language was used to generate each KAS based on the LOE and the balance of benefit versus harm of the findings. Topics that could not be researched via the stated approach were (1) definition of HTN in youth, and (2) definition of left ventricular hypertrophy. KASs related to these stated topics were generated via expert opinion. RESULTS: Nearly 15 000 references were identified during an initial literature search. After a deduplication process, 14 382 references were available for title and abstract review, and 1379 underwent full text review. One hundred twenty-four experimental and observational studies published between 2003 and 2016 were selected as primary references for KAS generation, followed by an additional 269 primary references selected between August 2015 and July 2016. The LOE for the majority of references was C. In total, 30 KASs and 27 additional recommendations were generated; 12 were related to the diagnosis of HTN, 13 were related to management and additional diagnostic testing, 3 to treatment goals, and 2 to treatment options. Finally, special additions to the clinical practice guideline included creation of new BP tables based on BP values obtained solely from children with normal weight, creation of a simplified table to enhance screening and recognition of abnormal BP, and a revision of the criteria for diagnosing left ventricular hypertrophy. CONCLUSIONS: An extensive and detailed systematic approach was used to generate evidence-based guidelines for the diagnosis, management, and treatment of youth with systemic HTN.

Updated Guideline May Improve the Recognition and Diagnosis of Hypertension in Children and Adolescents; Review of the 2017 AAP Blood Pressure Clinical Practice Guideline.

PURPOSE OF REVIEW: Hypertension in children and adolescents is under-recognized and under-diagnosed in clinical practice. The 2017 AAP Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents provides updated recommendations that may improve hypertension identification and management. RECENT FINDINGS: The AAP blood pressure guideline recommends annual screening for hypertension in children at preventive care visits and targeted routine screening in high-risk populations. A simplified blood pressure screening table is provided for easier recognition of blood pressures that may require attention. Normative blood pressure tables have been revised to include only data from normal-weight children as more representative of a healthy population. Classification of blood pressure in adolescents has been simplified to threshold values consistent with adult guidelines. The updated AAP blood pressure guideline has clarified and simplified recommendations for hypertension screening, diagnosis, and management based on a systematic review of current best evidence.

Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.

These pediatric hypertension guidelines are an update to the 2004 "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents." Significant changes in these guidelines include (1) the replacement of the term "prehypertension" with the term "elevated blood pressure," (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.

Management of severe hypertension in the newborn.

Blood pressure is considered a vital sign, as values too low or too high can be related with serious morbidity and mortality. In neonates, normal blood pressure values undergo rapid changes, especially in premature infants, making the recognition of abnormal blood pressures more challenging. Severe hypertension can occur in neonates and infants and is a medical emergency, often manifesting with congestive heart failure or other life-threatening complications. The cause or risk factors for the hypertension can usually be identified and may guide management. Most classes of antihypertensive medications have been used in the neonatal population. For severe hypertension, intravenous short-acting medications are preferred for a controlled reduction of blood pressure. In this article, we focus on identification, aetiology and management of severe hypertension in the newborn.

Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention, and Treatment of Pediatric Hypertension.

After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence.

Evidence-based guidelines for the management of hypertension in children with chronic kidney disease.

Hypertension is common in children with chronic kidney disease and early evidence suggests that it is a modifiable risk factor for renal and cardiovascular outcomes. Recommendations for blood pressure management in children with chronic kidney disease can be found in various clinical practice guidelines including the 4th Task Force Report, the European Society of Hypertension pediatric recommendations, and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the management of blood pressure in chronic kidney disease. Unfortunately, as pediatric trial evidence is limited, there are discrepancies in the recommendations that may lead to inconsistent clinical care and practice variation. This article reviews the strength of evidence behind each of the clinical practice guideline recommendations regarding blood pressure assessment, treatment targets, and first-line antihypertensive medications. The benefits and cautions of use of clinical practice guidelines are described with emphasis on the importance of reading beyond the summary statements.