Abstract
Background
Pediatric hypertension affects 3 % to 5 % of children and adolescents between ages 1 year to 18 years and may have long-term health consequences.
Aim of review
The purpose of this article is to review pediatric hypertension, including screening, methods of blood pressure measurement, etiology, evaluation, and treatment of patients with or without end-organ damage.
Key scientific concepts of review
In children, blood pressure levels are interpreted based on age, sex, and height to avoid misclassification. Blood pressure measurements at three separate visits are required to diagnose hypertension. Routine screening begins at age 3 years, but blood pressure is measured during each health visit in patients who have body mass index ≥95 %, take medications that increase blood pressure, or have health issues that may increase the risk of developing hypertension. The auscultatory method is preferred for blood pressure measurement in the right arm. A 24-h ambulatory blood pressure monitor is used to confirm hypertension and differentiate it from white-coat or masked hypertension. Primary (essential) hypertension is multifactorial and may be associated with overweight and obesity, genetic predisposition, premature birth, low birth weight, increased sodium intake, sedentary lifestyle, and obstructive sleep apnea. Secondary hypertension may be caused by specific diseases such as kidney disease, cardiovascular disease, endocrine abnormalities, adverse events from medication, and monogenic causes. Treatment for pediatric hypertension includes nonpharmacologic and pharmacologic therapies, including diet and lifestyle modification. Children with hypertension are more likely to have hypertension in adulthood and develop targeted end-organ injury of the brain, cardiovascular system, or kidneys. It is important to accurately diagnose and treat hypertension early in childhood to avoid long-term complications.
Graphical abstract
Highlights
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Hypertension affects 3 % to 5 % of children and adolescents.
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Blood pressure levels are interpreted based on age, sex, and height.
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Treatment varies with severity and includes diet and physical activity.
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Long-term complications include end-organ damage to the brain, heart, and kidneys.
1
Introduction
Pediatric hypertension (HTN) previously was rare but is becoming a growing problem with potential long-term health consequences. Pediatric blood pressure (BP) measurement and HTN became a focus for the medical community in the late 1970s with the report from the Task Force on Blood Pressure in Children [ ]. HTN affects 3 % to 5 % of children and adolescents between ages 1 year to 18 years [ ].
The current definition of pediatric HTN is based on the normal distribution of BP in healthy children [ ]. BP levels are interpreted based on age, sex, and height to avoid misclassification of children who are extremely short or tall. The BP measurements are repeated at three separate visits. In 2017, the American Academy of Pediatrics recommended that the definition of HTN for children aged ≥13 years would be the same as the definition in the adult HTN guidelines of the American Heart Association and American College of Cardiology [ ]. In these children, stage 1 HTN is defined as systolic BP between 130 and139 mm Hg or diastolic BP between 80 and 89 mmHg; stage 2 HTN is defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg [ ].
For children aged <13 years, the American Academy of Pediatrics uses the same definition of HTN as the European Society of Hypertension and Hypertension Canada [ ]. In these children, increased BP is defined as systolic BP or diastolic BP in the 90th to 94th percentiles; stage 1 HTN is defined as BP in the 95th to 99th percentiles; and stage 2 HTN is defined as BP ≥ 95th percentile plus 12 mmHg [ ]. The term prehypertension has been replaced by the term elevated BP, enabling alignment with the guidelines of the American Heart Association and American College of Cardiology [ ].
The diagnosis of HTN in neonates and infants is difficult and made during hospitalizations, including neonatal intensive care unit stays. Neonatal HTN is defined as systolic or diastolic BP ≥ 95th percentile for the postconceptional age on three separate measurements. It is difficult in neonates to make accurate BP measurements and the diagnosis of HTN because of the fluctuation in measured BP in the first few weeks after birth and small arm circumference [ ]. Acute severe elevation of BP is defined as a hypertensive emergency when there is associated new-onset or worsening organ damage or hypertensive urgency when there is no evidence of organ damage.
The purpose of this article is to review pediatric HTN, including screening, methods of BP measurement, etiology, evaluation, and treatment of patients with or without end-organ damage.
2
Pediatric hypertension prevalence and risk factors
The prevalence and alarm for pediatric HTN have been increasing in the past three decades [ ]. With the introduction of the American Academy of Pediatrics guidelines in 2017, the prevalence of pediatric HTN has doubled from 2 % to 4 % of children [ ]. Children who have BP that was reclassified into an advanced category may be overweight and have abnormal lipid and increased hemoglobin A 1c levels, indicating a prediabetic stage [ ]. Children who are overweight and obese have a prevalence of HTN between 3.8 % and 24.8 %, with obese patients being two times more likely to have HTN than children with healthy weight [ ]. Sex and race are also important risk factors for developing HTN, with a higher prevalence of HTN in boys than girls and Black and Hispanic than non-Hispanic White children.
3
Screening for hypertension
Current pediatric guidelines mandate starting BP measurement at age 3 years [ ]. If the patient is healthy and has normal BP, then BP is measured annually. However, BP is measured during all office visits in patients who have body mass index ≥95th percentile, take medications that increase BP, or have health issues that increase the risk of developing HTN [ ]. In addition, children aged <3 years who have an increased risk of developing HTN have BP measured at each well-child visit ( Table 1 ) [ ].
| Risk factors | Disorders |
|---|---|
| Birth issues | Premature birth Low birth weight |
| Cardiovascular | Coarctation of the aorta |
| Chronic illnesses | Diabetes Obstructive sleep apnea Vasculitis |
| Hematologic | Sickle cell disease |
| Kidney disease | Chronic kidney disease Glomerulonephritis Polycystic kidney disease Renal tumors |
| Transplants | Hematopoietic stem cell transplant Solid organ transplant |
4
Methods of blood pressure measurement in children
4.1
In-office blood pressure measurements
BP typically is measured from the right arm unless contraindicated by regional anatomic factors such as the presence of an arteriovenous fistula ( Table 2 ) [ ]. For accurate BP measurement, it’s very important to use the correct cuff size for patients arm size as mentioned in the above table. Small cuffs can overestimate BP, while large cuffs can underestimate BP. Children aged ≥3 years are seated, and children aged <3 years lie supine during BP measurement. When arm BP cannot be obtained, the child may lie prone for measurement of BP in the lower limbs. The auscultatory method is preferred for BP measurement in children. Correlation typically is good between oscillometric and auscultatory results, but when oscillometric measurement shows high BP, the measurement is repeated with the auscultatory method for confirmation.
| Step | Instructions |
|---|---|
| 1 | Child in a quiet room for 3 to 5 min before measurement Back supported Feet uncrossed on the floor |
| 2 | Measurement in the right arm for consistency b Arm at heart level, supported, and uncovered above the cuff |
| 3 | Use correct cuff size:
|
| 4 | Auscultatory blood pressure:
|
| 5 | Inflate cuff to 20 to 30 mmHg higher than pressure at radial pulse disappearance Avoid overinflation of cuff Deflate cuff 2 to 3 mmHg per second |
| 6 | Leg blood pressure:
|
b Right arm unless contraindicated by regional anatomic factors such as the presence of an arteriovenous fistula.
Automated office BP is another method of in-office BP measurement. This includes repeated BP measurement throughout intervals without the influence of an observer. The recording of BP begins with a five-minute rest, followed by a one-minute period of BP measurement. This cycle of a five-minute rest and one-minute measurement is repeated for three measurements. Automated office BP is the recommended method of in-office BP monitoring according to guidelines from Hypertension Canada 2020 and European Society of Hypertension [ , ].
4.2
Out-of-office blood pressure measurement
Out-of-office BP measurement is most commonly performed for 24 h with an ambulatory BP monitor. Ambulatory BP monitoring was initially used in the 1960s in adults. Over the past 6 decades, progress has been made with more advanced machines and applications to children.
In ambulatory BP monitoring, a portable device is worn that measures BP automatically at regular intervals, typically every 15 to 30 min during waking hours and school days and 20 to 30 min during sleep in children [ ]. An ambulatory BP monitoring device is used that is suitable for children and has been validated according to the American National Standards Institute, Association for the Advancement of Medical Instrumentation, and International Organization for Standardization [ ]. Various cuff sizes are available to ensure proper fit. Monitors are placed in the office to enable verification of accuracy. BP is measured with the device and compared with the resting in-office BP determined in the same arm with another validated device and using the same technique. Ambulatory BP monitoring in children has no serious adverse events, but poor tolerability is common in adolescents [ ].
Ambulatory BP monitoring is used to confirm elevated in-office BP and differentiate it from other BP phenotypes such as white-coat HTN, which is an exaggerated BP measurement caused by patient anxiety in the clinic ( Table 3 ). Ambulatory BP monitoring also assesses the circadian BP pattern that normally includes a BP decrease of 10 % to 20 % during sleep, which is known as dipping. Monitoring may identify non-dippers who have a BP decrease of <10 % during sleep. Furthermore, monitoring may identify masked HTN, which is the presence of HTN despite normal in-office BP.
| Patient characteristics | Indication |
|---|---|
| Office-confirmed hypertension | White-coat hypertension Blood pressure treatment evaluation |
| Coarctation of the aorta | Masked hypertension |
| Chronic kidney disease, including acquired solitary kidney | Masked hypertension Blood pressure treatment evaluation |
| Diabetes mellitus type 1 or 2 | Masked hypertension Detect abnormal circadian patterns |
| Genetic conditions predisposing to hypertension | Masked hypertension |
| Premature birth or low birth weight | Masked hypertension Abnormal circadian patterns |
| Obesity | Masked hypertension Abnormal circadian patterns |
Another method of out-of-office BP measurement is home BP monitoring. This depends on the ability of the patient or parent to make accurate measurements. Home BP monitoring may be most useful for adult patients who are being treated for HTN at home because it has high sensitivity despite low specificity. Pediatric guidelines typically suggest that home or school BP measurements in children may not be recommended for diagnosis but may be useful to monitor BP after the diagnosis of HTN [ ].
5
Etiology of hypertension
Pediatric HTN may be primary (also known as essential HTN) or secondary. Primary HTN is the most common type of HTN in children, and etiology is multifactorial, without a single underlying cause identified [ ]. In primary HTN, BP typically is elevated mildly in an older child, usually an adolescent with high body mass index and positive family history of HTN [ ]. In secondary HTN, BP is elevated secondary to a specific underlying etiology [ ]. Secondary HTN typically has higher elevation in BP (stage 2 HTN) and is more common in younger children, especially children aged <6 years who have normal body mass index [ ].
5.1
Primary HTN
Pediatric primary HTN is associated primarily with overweight and obesity and genetic predisposition, and other associated factors include history of premature birth, low birth weight, increased sodium intake, sedentary lifestyle, and obstructive sleep apnea [ ]. Primary HTN may be attributed to changes in multiple body system mechanisms such as the renin-angiotensin-aldosterone system, regulation of vasodilation and vasoconstriction, endothelin regulation, and sympathetic nervous system activation [ , ]. Primary HTN is highly correlated with childhood obesity and may become a lifelong health problem. In the United States, 20 % of children aged 2 to 19 years are overweight or obese, and hypertensive children are more likely to remain hypertensive into adulthood and sustain targeted organ injury, including left ventricular hypertrophy and vascular stiffening [ ]. HTN may occur in 24 % of obese children versus 2 % to 4 % of nonobese children [ ]. Although the pathophysiology of obesity-associated HTN is not well understood, insulin resistance and hyperinsulinemia may cause renal sodium reabsorption and increased sympathetic nervous system activity [ ].
Genetic factors may contribute to primary HTN. Children who have a family history of HTN may have a high risk of developing primary HTN before age 18 years [ ]. The inheritance pattern for HTN is variable and modified by environmental and lifestyle factors. Primary HTN may be associated with a positive family history, and patients typically are older than age 6 years and overweight [ ]. In adolescents who have normal weight and waist circumference, a positive family history increases the risk of developing HTN. These normotensive adolescents may have increased BP levels and impaired arterial elasticity. The age of onset and severity of HTN also may be affected by lifestyle choices, environmental factors, and genetic sensitivity.
5.2
Secondary HTN
Secondary HTN may be caused by specific diseases such as kidney disease, cardiovascular disease, endocrine abnormalities, adverse events from medication, and monogenic causes. Secondary HTN, albeit less common than primary HTN, is important because it may be associated with increased risk of morbidity and mortality [ ].
Renal causes of HTN typically include vascular or parenchymal diseases. Renovascular diseases are most common and manifested by abnormal narrowing or obstruction of renal vasculature, which may occur in renal artery stenosis, thrombotic microangiopathies, including hemolytic uremic syndrome, and vasculitis [ ]. The most common renovascular cause of secondary HTN in children is nonatherosclerotic renal artery stenosis secondary to fibromuscular dysplasia, which causes 5 % to 10 % of all cases of pediatric HTN [ ]. Decreased renal perfusion may cause increased release of renin and associated HTN. Renal artery stenosis in children usually occurs with small branch stenosis, which makes diagnosis more difficult than in adults who have stenosis of the main renal artery [ ]. The recommended initial screening test for renal artery stenosis is Doppler ultrasonography because it is commonly available, noninvasive, and has good sensitivity (75 %) and specificity (90 %) [ ]. Angiography with computed tomography or magnetic resonance imaging may have higher sensitivity and specificity than ultrasonography but may be less commonly available and more expensive, requires the use of contrast medium, and usually requires sedation. Diagnostic digital subtraction angiography may be performed with therapeutic angioplasty or stenting but has a high rate of complications such as stoke, groin hematoma, and contrast associated kidney injury [ ].
Renal parenchymal diseases associated with HTN include glomerulonephritis, polycystic kidney disease, and chronic kidney disease. HTN associated with chronic kidney disease typically occurs from fluid overload and activation of the renin-angiotensin-aldosterone system. In addition, patients with kidney failure may have decreased expression and serum levels of renalase, which is an amine oxidase expressed primarily by kidneys. Renalase normally degrades circulating catecholamines and causes decreased BP and decreased sympathetic tone. Therefore, renalase deficiency may contribute to sympathetic overactivity and hypertension observed in chronic kidney disease patients [ ].
The most common cardiac disease associated with secondary HTN is coarctation of the aorta, which is a narrowing of the aorta most commonly distal to the origin of the left subclavian artery. Coarctation of the aorta represents 5 % to 8 % of congenital heart disease and may present in neonates with shock and left ventricular dysfunction or older children with upper limb HTN [ ]. The elevated BP proximal to the aortic narrowing occurs from physiologic compensation to maintain adequate distal perfusion. This results in a typical clinical finding in children during examination when arm to leg systolic BP difference is >20 mmHg (differential BP), and there is delayed or absent femoral pulse (radio-femoral delay). The mechanism of HTN in children with coarctation of the aorta includes anatomic narrowing, decrease arterial compliance, impaired endothelial function, and abnormalities of the renin-angiotensin-aldosterone system [ ]. In 17 % to 77 % of children, after repair of coarctation of the aorta, HTN may occur because of incomplete repair, recurrence, or decreased arterial compliance caused by remodeling [ , ]. Diagnosis of coarctation of the aorta is made with an echocardiogram, which may show narrowing of the aortic arch and increased Doppler flow velocity ( Fig. 1 ). Computed tomography and magnetic resonance imaging scans also provide detailed images of aortic arch anatomy [ , ].
