Evaluation and Management of Hypertension in Childhood

Written by

Joseph T. Flynn, M.D.

Director, Pediatric Hypertension Program

Division of Pediatric Nephrology

Montefiore Medical Center

111 East 210^th Street

Bronx, NY 10467

Fax: 718.652.3136

And modified by Ellin Lieberman, M.D.

The most commonly used definitions of normal and abnormal blood pressure (BP_) in childhood were published in the Second Task Force Report (2). Data from 9 studies involving 70,000 children in the United States and United Kingdom were summarized, and age-specific BP percentile curves were generated. Normal BP was defined as systolic and diastolic BP readings below the 90th percentile for age, and hypertension was defined as systolic and diastolic BP readings > 95th percentile for age. To avoid over-diagnosis of hypertension, and because the incidence of hypertension in childhood is < 5% (4,5), at least 3 abnormal readings, obtained on separate occasions, should be obtained before considering a diagnosis of "hypertension" in an individual patient.

The Second Task Force data have been refined and height is thought to be the most important variable in determining whether a particular child has an elevated BP. . The actual definitions of normal BP and hypertension from the Second Task Force report were retained, but new tables of normal BP levels based on height percentiles were made(Tables 1 and 2).

Defining normal BP in infants, particularly newborns, is more difficult; it was reviewed in elsewhere (7).

Importance of Identifying Hypertensive Children - Blood Pressure Tracking

What does it mean if a child has one or a few elevated BP readings? Do these children need specific follow-up?

Data are not definitive; however, many authors argue that such children may be destined for adult high BP.. This concept,is known as BP “tracking” has extensively studied. (8-11),

One important study is the Muscatine study (8), [ 2445 children aged 7‑18y in Muscatine, Iowa had family histories, BP, and other vital signs such as height and weight recorded between 1971‑8. A group of them was then restudied as young adults (age 23-28y) for repeat assessment. Those who had systolic BP > the 90^th percentile in childhood were 4 times more likely to develop adult hypertension than subjects without elevated systolic BP in childhood. Subjects with diastolic BP > t90^th percentile in childhood were twice as likely to develop adult hypertension .Furthermore, the likelihood of developing adult hypertension increased with increasing numbers of childhood readings > 90^th percentile, and the absence of abnormal readings in childhood was associated with a reduced risk of developing adult hypertension. Other important influences on adult BP were body mass and a positive family history of hypertension.

Etiology of Hypertension in Children

Overall, most childhood hypertension is secondary; that is, caused by another underlying disorder, which in most cases will be renal disease (14-18; Table 3). Essential or primary hypertension becomes more prevalent with increasing age. The distribution of causes of childhood hypertension seen at a specific center or by a given practitioner varies according to the practice setting (primary vs. referral The diagnostic challenge in the non-referral setting therefore becomes making sure that children with secondary causes of hypertension are not diagnosed as having essential or primary

hypertension.

As with the definition of hypertension, infants (< one year of age) are a unique population with respect to the causes of hypertension. Coarctation of the aorta and renovascular disease constitute the most frequent causes of hypertension (Table 3), with other diagnoses such as structural renal disease and bronchopulmonary dysplasia also being relatively frequent (7). Most infants with renovascular hypertension have a history of umbilical catheter placement (15),

Evaluation of the Child with Suspected Hypertension

One of the most important steps in the evaluation of children with suspected hypertension is to ensure that the BPs being measured correctly (2). A conventional mercury column or aneroid sphygmomanometer should be used in school-aged children and teenagers. Although less accurate, an automated, oscillometric device such as the Dynamap® (Critikon Inc., Tampa, FL), can be used in infants and toddlers who will not cooperate with manual BP determinastion.

The bladder of the cuff should encircle 80-100% of the circumference of the upper arm, and its width should be at 40% of the upper arm circumference (3). Since too narrow of a cuff will create false reading, children with longer upper arms than others of the same age require a wider cuff. Not to be overlooked is a large adult or thigh cuff for use in obese children. The child should be seated quietly for at least 5 minutes prior to BP determination. The arm should be supported at heart level. Infants' blood pressures should be obtained in the supine position. The disappearance of the 5th heart sound is now preferred for the diastolic reading (3).

If a child has been a persistently elevated BP, the first step is to obtain a thorough history, which

usually begins with asking whether any symptoms suggestive of hypertension exist such as headaches, dizziness, diplopia, vomiting, or nosebleed. The interview should then focus on whether symptoms of another underlying disorder are present, including symptoms of underlying renal disease (enuresis, gross hematuria, edema, fatigue), heart disease (chest pain, exertional dyspnea, palpitations), or diseases affecting other organ systems (endocrinologic, rheumatologic, etc.). The past history should include recent as well as chronic illnesses, prior hospitalizations or episodes of trauma, recurrent urinary tract infections or unexplained fevers and neonatal history of umbilical line placement (in infants). A family history of hypertension, diabetes, renal disease and other cardiovascular disease (hyperlipidemia, stroke) should be obtained.. Finally, it is important to ask about over-the-counter, prescription and illicit drug use, as many agents can either cause or exacerbate hypertension.

Physical examination includes the child’s height and weight percentiles. Following this, 4 extremity

BP are taken; The remainder of the physical examination should focus on discovering specific findings that may provide clues to the etiology and/or degree of hypertension. Common examples of such findings are listed in Table 4.

Many hypertensive children have normal physical examinations, even in the presence of significant underlying renal or other organ system disease. Therefore, laboratory testing is usually necessary in order to complete the child’s evaluation. Before starting

on laboratory testing, however, the child’s age, history, physical exam findings, and degree of blood pressure elevation should be used to decide what are the best studies for the particular child. Dividing the laboratory evaluation into screening, specific and specialized phases as outlined in Table 5 is helpful .

All hypertensive children should undergo the screening laboratory tests listed. These can easily be obtained in most primary care office settings or in community hospitals, and will usually detect whether significant renal disease or another chronic illness is present. Of the more specific tests, only those indicated by the history, physical examination and screening tests should be obtained. For example, chest radiographs need only be obtained in hypertensive children with heart murmurs, or those with a gradient of more than 30 mmHg between the upper and lower extremity BP

An exception would be the echocardiogram, which should be obtained in any hypertensive child because left ventricular hypertrophy can be present even in children with mild hypertension (21,22). On the other hand, renal ultrasounds probably only need to be obtained in preadolescent children with hypertension, and in hypertensive adolescents with abnormal urinalyses or unusually severe hypertension. It may be helpful to consult a specialist with experience in pediatric hypertension at this stage of the evaluation, especially if one or more of the screening studies was abnormal.

The specialized studies listed in Table 5 are typically done at referral centers, or by pediatric sub-specialists with extensive experience managing hypertensive children. Several of these are used to investigate the possibility of renal artery stenosis, which as discussed earlier is a relatively common cause of hypertension in children with secondary hypertension (Table 3). While a detailed discussion of the relative merits of these procedures is beyond the scope of this review, it is important to note that since renal artery stenosis in children is typically caused by fibromuscular dysplasia (23), angiography is still the gold standard for diagnosis because of its superior ability to detect branch vessel disease, especially in infants and young children (24). Magnetic resonance angiography, which is finding increased use for evaluation of hypertension in adults (25) may have a role in the adolescent or older child who can cooperate with the procedure. However, if the magnetic resonance angiogram reveals the presence of renal artery stenosis, the child may still need to undergo an angiogram prior to revascularization surgery.

One other diagnostic study that deserves specific mention is ambulatory blood pressure monitoring (ABPM). In this procedure, the subject wears a blood pressure cuff that takes BP at regular intervals for an entire day. Lightweight devices and a variety of cuff sizes are widely available, making it possible to obtain ABPM studies in young children as well as teenagers (25).

Finally, no diagnostic evaluation of a hypertensive child would be complete without including one or more studies to assess for the presence of end-organ damage (29). Although hypertension itself is virtually unknown as a cause of chronic renal failure in childhood, both left ventricular hypertrophy and retinal changes are relatively common, even in children with essential hypertension (21,22,30). As will be discussed later, if such abnormalities are present, the child will likely require antihypertensive drug treatment.

Treatment of childhood hypertension

effective treatment of hypertensive children requires a comprehensive approach incorporating patient/family education, non-pharmacologic measures, and antihypertensive medications, as well as monitoring for medication side effects and treatment response. This can be a time-consuming endeavor but it is essential to include all components, as hypertension can be a lifelong problem for many children and adolescents, particularly those with secondary forms of hypertension.

Generally, treatment should begin with non-pharmacologic measures such as weight loss, aerobic exercise and dietary modifications such as sodium restriction (2,3,29). Obese children clearly respond well to weight loss; both systolic and diastolic blood pressure reduction has been demonstrated in controlled settings (31,32). Unfortunately, successful weight loss is difficult to achieve, especially in the primary care setting. It may be appropriate to refer such children to comprehensive weight loss programs that include not only nutritional intervention, but also exercise and family counseling (33,34). Exercise is frequently recommended as a treatment for hypertension, and clearly does have a role in the management of hypertensive children (29,35). Reviews of the effects of exercise on blood pressure have demonstrated a blood pressure-lowering effect in both normotensive and hypertensive individuals (36). It is important to emphasize that aerobic exercise activities such as running, walking, or cycling are the preferred forms of exercise in the management of hypertension, as static exercise activities can lead to dangerous acute blood pressure elevation (35). It is usually possible to find some form of aerobic exercise that the child enjoys and incorporate it into the child’s treatment plan. Frequently the child is already participating in an appropriate activity on occasion and will only need to increase the amount of time they spend in that activity to achieve an antihypertensive effect.

The role of dietary modification in the treatment of hypertension has received a great deal of attention, most of which has focused on the role of sodium. Whether or not excessive sodium intake actually causes hypertension is a still unresolved debate (37). However, many individuals with hypertension, children included, are “salt-sensitive,” and will probably benefit from a reduction in their sodium intake (38,39). Other dietary constituents that have been examined with respect to hypertension include potassium and calcium, both of which have been demonstrated to have antihypertensive effects (39-43). Therefore a diet that is low in sodium content but enriched in potassium and calcium may be even more effective than a diet that restricts sodium only. An example of such a diet is the so-called “DASH” diet, which has been shown to have a clear blood pressure-lowering effect in adults with hypertension, even in those receiving antihypertensive medication (44). Although this diet has not been specifically studied in children, if used under the supervision of a registered pediatric dietitian, the basic elements of the DASH diet should be easily adaptable to the treatment of hypertensive children. The DASH diet also incorporates measures designed to reduce dietary fat intake, an important strategy given the frequent presence of both hypertension and elevated lipids in children and adolescents (13).

Deciding which children require antihypertensive drug treatment is the most crucial step in the management of children with hypertension. Generally, any child with symptomatic hypertension, end organ damage, or who fails non‑pharmacologic measures deserves drug therapy (29,45). Other factors such as the presence of obesity and/or a family history of hypertension may also influence the decision to treat. The following quote from the Second Task Force Report (2) is appropriate to keep in mind whenever contemplating starting a child on antihypertensive medications: "Major questions still remain unresolved with regard to the long‑term effects of drug treatment on children and adolescents…a definite need must be established before [antihypertensive] therapy...is introduced during the 1st or 2nd decade of life." Given this, consultation with a specialist experienced in managing childhood hypertension is recommended at the initiation of drug therapy.

Some general principles should be followed in the treatment of hypertensive children when drug therapy is deemed necessary. First and foremost of these is that non-pharmacologic measures should be incorporated into every hypertensive child’s treatment plan. As noted above, weight loss, aerobic exercise and dietary modifications can play an important role in the management of hypertension. The second important principle is that drug therapy should be designed to maximize compliance and minimize adverse effects. This means that drugs with longer duration of action should be chosen over those with shorter duration, and that agents with predictable adverse effects should be avoided (for example, avoidance of diuretics in teen athletes).

As in adults, the “stepped care” approach has been recommended for children treated with antihypertensive medications (2,29,45,46). Utilizing this approach, the dose of the initial agent chosen is increased until either the blood pressure is controlled, the maximal dose is reached or side effects appear, then a second agent of a different pharmacologic class added and its dose increased as with the first agent, and so on. If possible, the initial agent chosen should be directed at the underlying pathophysiology of the child’s hypertension (45); for example, a vasodilator or diuretic would be appropriate in the case of hypertension related to acute glomerulonephritis. The goal of treatment should be reduction of blood pressure to below the 90th percentile for age and gender (2). As noted above, effective therapy should also be designed to maximize compliance and minimize side effects.

A challenge perhaps more significant than deciding which child to treat with antihypertensive medications is the decision of which agent to choose as the initial agent, particularly in children with essential hypertension. Whereas there are many studies comparing different antihypertensive regimens in adults, no such comparative studies have ever been conducted in children. Although a few studies of the efficacy and safety of antihypertensive medications in children have been published, until recently most of these data have been retrospective in nature (47,48). Furthermore, pediatric dosing recommendations have been published for only a handful of agents, mostly older agents that have fallen out of favor in the modern management of hypertension (48,49). Given this, it is difficult to make specific recommendations at this juncture, other than to note that recent publications have focused on calcium channel antagonists and angiotensin converting enzyme inhibitors as suitable initial choices (3,45,46). Recommended pediatric doses for selected antihypertensive agents are listed in Table 6. As noted in the table, there are very few commercially available suspension formulations of antihypertensive medications, which has lead to frequent compounding of so-called "extemporaneous" suspensions for use in infants and younger children; fortunately, stability data for some of these suspensions have recently been published (50,51).

Important adjunctive aspects to the drug therapy of childhood hypertension include ongoing monitoring of blood pressure (especially home blood pressure monitoring), surveillance for medication side effects, periodic monitoring of electrolytes in children treated with angiotensin converting enzyme inhibitors or diuretics, counseling regarding other cardiovascular risk factors, and continual emphasis on non-pharmacologic measures. It may also be appropriate to consider "step‑down" therapy in selected patients. This involves an attempt at gradual reduction in medication after an extended course of good blood pressure control, with the eventual goal of completely discontinuing drug therapy. Children with essential hypertension, especially obese children who successfully lose weight, are the best candidates for the step-down approach. Such patients usually require continued blood pressure monitoring after the cessation of drug therapy, as well as continued non-pharmacologic treatment.

Finally, there are some children who will require surgical intervention for their hypertension. Such patients are typically those with renovascular hypertension, aortic coarctation, or other secondary forms of hypertension. They should be referred to a children’s hospital or other tertiary center where appropriate pediatric surgical and medical specialists are available.

Conclusions

Blood pressure elevation in childhood may be the first clue to underlying renal or other organ system pathology, or simply a warning sign of future cardiovascular risk. Careful measurement of blood pressure and thorough evaluation of children with sustained blood pressure elevation should allow identification of those who require treatment. While few data exist regarding the optimal agents for treatment of hypertensive children, usually a combination of pharmacologic and non-pharmacologic measures will result in satisfactory control of hypertension while allowing a normal quality of life.
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Legend to Table 1:

¹Reproduced by permission of Pediatrics (Ref. 2).

²Height percentile as determined by standard growth curves

Legend to Table 2:

¹Reproduced by permission of Pediatrics (Ref. 2).

²Height percentile as determined by standard growth curves
Table 3. Causes of Childhood Hypertension by Age Group¹

	Infants^2	School-age	Adolescents
Primary/Essential	<1%	15-30%	85-95%
Secondary	99%	70-85%	5-15%3
Renal Parenchymal Disease	20%	60-70%
Renovascular	25%	5-10%
Endocrine	1%	3-5%
Aortic Coarctation	35%	10-20%
Reflux Nephropathy	0%	5-10%
Neoplastic	4%	1-5%
Miscellaneous	20%	1-5%

Legend to Table 3:

¹Adapted from references 7,14-18.

²Less than one year of age.

³Breakdown of causes is generally similar to that for school-age children.

Table 4. Physical Exam findings in Childhood Hypertension

	Finding	Possible Etiology
Vital Signs	Tachycardia Decreased LE pulses; drop in BP from UE’s to LE’s	Hyperthyroidism, Pheochromocytoma, Neuroblastoma, Essential Hypertension Aortic Coarctation
Height/weight	Growth retardation Obesity Truncal obesity	Chronic renal failure Primary hypertension Cushing’s syndrome
Head & Neck	Moon facies Elfin facies Webbed neck Thyromegaly	Cushing’s syndrome Williams syndrome Turner’s syndrome Hyperthyroidism
Skin	Pallor, flushing, diaphoresis Acne, hirsutism, striae Cafe-au-lait spots Adenoma sebaceum Malar rash	Pheochromocytoma Cushing’s syndrome, anabolic steroid abuse Neurofibromatosis Tuberous sclerosis Systemic Lupus Erythematosus
Chest	Widely spaced nipples Heart murmur Friction rub Apical heave	Turner’s syndrome Coarctation Systemic Lupus Erythematosus (pericarditis) Left ventricular hypertrophy/chronic hypertension
Abdomen	Mass Epigastric/flank bruit Palpable kidneys	Wilms’ tumor, Neuroblastoma, Pheochromocytoma Renal artery stenosis Polycystic kidney disease, hydronephrosis, Multicystic-dysplastic kidney
Genitalia	Ambiguous/virilization	Adrenal hyperplasia
Extremities	Joint swelling Muscle weakness	Systemic Lupus Erythematosus Hyperaldosteronism, Liddle’s syndrome

Legend to Table 4:

Abbreviations used in table: BP, blood pressure; LE, lower extremity; UE, upper extremity.

Table 5. Laboratory evaluation of the child with hypertension

Phase	Studies
Screening tests	Urinalysis and culture Electrolytes, BUN, creatinine, glucose, calcium, phosphorus, uric acid Lipid panel (cholesterol, triglycerides, etc.) CBC with differential, platelet count
Specific tests	24 hour urine collection for protein excretion & creatinine clearance Urine and serum catecholamines Hormone levels (thyroid, adrenal, etc.) Echocardiogram Renal ultrasound
Specialized studies	Renin profiling (plasma renin & 24 hour urinary sodium excretion) Renal ultrasound with Doppler study of renal arteries Captopril challenge test Renal angiography with renal vein renins Magnetic resonance angiography Captopril renal scan Ambulatory blood pressure monitoring Renal biopsy

Table 6. Antihypertensive agents useful for chronic treatment of childhood hypertension¹

Class	Drug	Starting Dose	Usual Interval^2	Maximum Dose	Other Comments
ACEI's	Captopril^3	0.5-1.0 mg/kg/dose	TID	6 mg/kg/day	Cough and hyperkalemia may occur
	Enalapril	0.2 mg/kg/dose	QD-BID	1 mg/kg/day up to 40 mg/day	As above
	Lisinopril	0.2 mg/kg/day	QD-BID	1 mg/kg/day	As above
AT receptor antagonist	Losartan	25 mg/day	QD-BID	100 mg/day	No pediatric data available
a/b antagonist	Labetalol^3	2-3 mg/kg/day	BID	10-12 mg/kg/day up to 2.4 g/day	Relatively weak alpha effect in oral formulation
b-antagonists	Atenolol	0.5-1 mg/kg/day	QD-BID	2 mg/kg/day	Cardioselective; monitor for bradycardia