Hypertension in Children

Background

In the mid-1970s, the National High Blood Pressure Education Program (NHBPEP) of the National Heart, Lung, and Blood Institute (NHLBI) examined the available blood pressure distribution in healthy children and defined the upper limit of normal blood pressure in children.

The report, known as the first report, was published in 1977.

Major updates of this report were conducted in 1987, 1996, and 2004; these updates are referred to as the second, third, and fourth reports, respectively.

In 2017, the AAP supported the development and published new clinical practice guidelines for hypertension in children, referred to as the fifth report, using recommendations from the Institute of Medicine.

Definition of Terms

Hypertension is defined as Systolic and/or Diastolic Blood Pressure ≥ 95th percentile for age, sex, and height or Systolic Blood Pressure ≥ 130/80 mmHg for children above 13 years of age on three or more occasions.

White coat hypertension (WCH) is a condition where blood pressure in the clinic setting is high while the BP during Ambulatory Blood Pressure Measurement is normal. This occurs due to a pressor response in the medical setting.

Masked HTN (MH) is characterized by high Ambulatory BP in the presence of normal Blood Pressure in the clinic. Previously referred to as “reverse WCH” or “WC normotension,” Masked Hypertension has been associated with more extensive target organ damage than is seen in true normotensive subjects.

Ambulatory Blood Pressure Measurement (ABP) is a 24-hour Blood Pressure Measurement with two-hourly measurements recorded. It assesses diurnal variation in blood pressure and is considered more reliable than other methods. Values based on ABP correlate better with organ damage.

• Hypertension prevalence: Uncommon in infants and younger children (˂ 1%).
• Severe symptomatic Hypertension: Usually secondary.
• Rising prevalence: Linked to increasing rates of obesity.
• Global prevalence (1994 – 2018): 4% in those 19 years and younger.
• Age-specific prevalence: Ranging from 3.28% (age 19) to 7.89% (age 14).
• Africa prevalence (1996 – 2017): Overall 5.5%, with regional variations.
• Regional prevalence: Central (9.8% - 10.1%), Eastern (6.5% - 17.1%), Northern (4.8% - 19.7%), Southern (4.5% - 21.2%), Western (0.2% - 24.8%).
• Relationship with BMI: Notable BP increase with higher BMI.
• Nigeria prevalence: Ranged from 2.3% to 10.2% across the country.
• Zaria prevalence (2005): 2.8% (Bugaje et al.).

Determinants of Hypertension

• Age
• Height
• Gender
• Race
• Birth weight
• Nephron number
• Lifestyle
• Obesity
• Salt intake
• Calcium and potassium supplementation
• Sleep-disordered breathing

Hypertension can be classified as either primary, with no identifiable cause, or secondary, where an underlying cause is identified.

Most cases of secondary hypertension result from pathologies in other organs, which can include:

1. Kidneys and their vessels
2. Adrenal glands
3. Thyroid gland
4. Heart

Causes of Hypertension in Children

Renal

• Renal parenchymal disease
• Renal vascular disease

Cardiovascular

• Coarctation of the Aorta
• Conditions with large stroke volume (PDA, AV Fistula)

Endocrine

• Hyperthyroidism
• Excessive catecholamines (Pheochromocytoma)
• Adrenal Dysfunction (CAH 11B, 17A hydroxylase deficiency, Cushing Syndrome), Obesity
• Hyperaldosteronism (Conn’s, Renin-producing tumors)
• Hyperparathyroidism

Neurogenic

• Raised ICP (Intracranial Pressure)

Drugs/Chemicals

• Sympathomimetics
• Steroids
• Amphetamines
• Lead

Miscellaneous

• Hypercalcemia

Common causes of childhood Hypertension by age group

Age Group	Causes
Neonates	Renal Vein Thrombosis, Umbilical Artery Catheterization
Children	Renal disease, Coarctation of Aorta, Endocrine diseases, Drugs
Adolescents	Essential Hypertension

Appropriate Cuff Size:

• The cuff bladder length should be between 80% and 100% of the arm circumference.
• The width of the cuff should be 40% of the arm circumference, measured at the midpoint between the acromion and olecranon.

Procedure:

• Inflate the cuff to a pressure 20–30 mm Hg above the point where the radial pulse disappears. Avoid overinflation.
• Deflate the cuff at a rate of 2–3 mmHg per second.
• Record the first audible sound (phase I Korotkoff) as the Systolic Blood Pressure (SBP).
• Record the last audible sound (phase V Korotkoff) as the Diastolic Blood Pressure (DBP).

Measurements should be rounded to the nearest 2 mmHg.

Blood Pressure Check Recommendations

Fifth Report (Latest Recommendation):

An annual blood pressure check is recommended for otherwise healthy children above 3 years of age.

Fourth Report:

In the fourth report, blood pressure checks were recommended for children 3 years of age and older at all healthcare encounters, including well-child care or sick visits.

Additionally, certain children younger than 3 years with comorbid conditions should also have their blood pressure monitored. These conditions include:

• Prematurity
• Low birth weight (LBW) infants
• Congenital heart or genitourinary anomalies
• Recurrent urinary tract infections (UTI)
• Hematuria or proteinuria
• Malignancy
• Certain medications
• Systemic illness associated with hypertension

Basic Evaluation:

• Serum electrolyte, urea, creatinine
• Full blood count
• Urinalysis and Urine culture
• Renal ultrasound with Doppler

Evaluation for Comorbidity:

• Fasting Lipid profile
• Fasting glucose

Evaluation for End-Organ Damage:

• Echocardiogram
• Retinal exam

Goals of Treatment

General:

• Blood pressure less than the 90th percentile for age, sex, and height
• Or
• Blood pressure less than 130/80 mmHg
• Whichever is lower of the above based on office/casual BP reading.

For patients with CKD:

• Ambulatory Blood Pressure Monitoring (ABPM) is recommended
• A 24-hour Mean Arterial Pressure (MAP) less than the 50th percentile is recommended.

Non-pharmacological Treatment

• Weight reduction.
• Regular physical activity.
• Dietary modification

DASH diet: consumption of more fruits, vegetables, fiber, non-fat dairy, reduced sodium intake (1.2g/day in younger children and 1.5g/day in older children)

General Guidelines to Pharmacotherapy

Indications:

1. Persistent hypertension despite lifestyle modifications, especially with an abnormal echocardiogram; Symptomatic hypertension
2. Stage 2 hypertension without a modifiable risk factor
3. Any stage of hypertension in patients with diabetes mellitus or CKD

Principles:

1. Monotherapy is advocated at inception using the lower dose range.
2. The dose could be increased in a step-wise manner until the maximum tolerable dose
3. Initial agent could be replaced with a member from another class.
4. Another agent that has complementary action could be added because of additive effect and the need to reduce the chances of evolution of dose-dependent adverse effect.

Recommended doses for selected Antihypertensive agents in children and adolescents

Class	Drug	Dose	Maximum Dose
Aldosterone Receptor Antagonist	Spironolactone	1 mg/kg/day qd-bid	100 mg/day
ACE Inhibitors	Captopril	0.5 mg/kg/day (0.05 mg/kg/dose in infants) tid	450 mg/day
	Lisinopril	0.07 mg/kg/day qd	40 mg/day
ARB	Losartan	0.75 mg/kg/day qd	100 mg/day
Alpha and Beta-Adrenergic Blockers	Labetalol	2-3 mg/kg/day bid	1.2 g/day
	Carvedilol	0.1 mg/kg/dose bid	25 mg bid
Beta-Adrenergic Antagonists	Atenolol	0.5-1 mg/kg/day qd-bid	100 mg/day
	Propranolol	1 mg/kg/day bid-tid	640 mg/day
Calcium Channel Blockers	Amlodipine	1-5 years: 0.1 mg/kg/day; >6 years: 2.5 mg/day qd	1-5 years: 5 mg/day >6 years: 10 mg/day
Central Alpha Agonist	Clonidine	5-10 μg/kg/day bid-tid	0.9 mg/day
Diuretics	Furosemide	0.5-2.0 mg/kg/day qd-bid	6 mg/day
	HCTZ (Hydrochlorothiazide)	0.5-1 mg/kg/day qd	37.5 mg/day
Vasodilators	Hydralazine	0.25 mg/kg/dose tid-qid	200 mg/day
	Minoxidil	0.1-2 mg/kg/day bid-tid	50 mg/day

Antihypertensives used for severely hypertensive patients with less significant symptoms

Class	Drug	Dose	Route	Remarks
Central Agonist	Clonidine	0.05-1.0 mg/dose, may be repeated up to 0.8 mg total dose	PO	Side effects include dry mouth and drowsiness
Direct Vasodilator	Hydralazine	0.25 mg/kg/dose, up to 25 mg/dose	PO	Extemporaneous suspension stable only for a week
	Minoxidil	0.1-0.2 mg/kg/dose, up to 10 mg/dose	PO	Most potent vasodilator; long-acting
Dopamine Agonist	Fenoldopam	0.2-0.8 μg/kg/min	IV infusion	Modest reduction in blood pressure in pediatric age group
Calcium Channel Blocker	Isradipine	0.05-0.15 mg/kg/dose, up to 5 mg/dose	PO	Stable suspension, can be compounded

Antihypertensives for Severely Hypertensive Patients with Life-Threatening Symptoms

Class	Drug	Dose	Route	Remarks
Beta-Adrenergic Blocker	Esmolol	100-500 μg/kg/min	IV infusion	Very short-acting, may cause profound bradycardia
Direct Vasodilator	Hydralazine	0.2-0.4 mg/kg/dose	IV, IM	Given every 4 hours if bolus
	Sodium Nitroprusside	0.5-10 μg/kg/min	IV infusion	Monitor levels if given for >72 hours or in renal failure
Alpha- and Beta-Adrenergic Blocker	Labetalol	Bolus: 0.2-1 mg/kg/dose, up to 40 mg/dose Infusion: 0.25-3.0 mg/kg/hr	IV bolus or Infusion	Asthma and overt heart failure are contraindications
Calcium Channel Blocker	Nicardipine	Bolus: 30 μg/kg, up to 2 mg/dose Infusion: 0.5-4 μg/kg/min	IV bolus or Infusion	May cause reflex tachycardia

Hypertensive Emergency

A spectrum of clinical presentation where uncontrolled BP leads to end-organ dysfunction with BP elevation ≥ 30 mmHg above the 95th percentile. Examples include CVA (Cerebrovascular Accident), AKI (Acute Kidney Injury), LVD (Left Ventricular Dysfunction), retinopathy, malignant hypertension.

Treatment: Admit to the ICU!

• BP should be lowered aggressively over minutes to hours.
• Reduce BP by 25-30% in the first 8 hours, then to normal in the next 24 - 48 hours.
• Precipitous drop in BP can result in impairment of perfusion of vital organs.
• Use parenteral very short-acting antihypertensives.

Monitoring/Follow-Up

Patients treated with drugs should have follow-up every 4 – 6 weeks for dose adjustments until the target BP is achieved, then 3 – 4 monthly follow-up visits.

Those on lifestyle modification only should have 3 – 6 monthly visits.

The major points of the 2017 AAP CPG are:

• Change in HTN categorization
• Revised BP tables and screening tables
• Use of ABPM
• Lower treatment goals

The cutoff point for hypertension in children and adolescents is lower than the previous cutoff points in the fourth report. The new guideline is based on evidence-based data, excluding children who are overweight and obese.

Emphasis is placed on 24-hour ABPM as a way to diagnose children and adolescents with masked hypertension, which is associated with target organ damage. It is also useful for monitoring BP in children with CKD.

Except in children with co-morbidities and underlying conditions with an increased risk of hypertension, monitoring of blood pressure in otherwise well children greater than 3 years should be done annually.

The goal of treatment is to attain lower blood pressure levels for all hypertensives, with even lower values for those with CKD. Monotherapy, rather than multi-drug therapy, is advocated, and doses should be increased in a step-wise approach until the target BP is attained.

Echocardiography is only recommended when drug therapy is being considered and not routinely in all hypertensive children or adolescents.

Hypertension is a silent killer; hence, early diagnosis and the institution of appropriate management can significantly prevent morbidity and mortality. More pertinent is the prevention of hypertension through lifestyle modification, particularly for those with risk factors for hypertension.

The 2017 AAP CPG addresses aspects of the evaluation and management of high BP in children and adolescents based on a strict evidence-based approach, as recommended by the NHLBI. It is the first to be aligned as much as possible with the new guidelines for adults.