OVERVIEW: What every practitioner needs to know

Are you sure your patient has hypertension? What are the typical findings for this disease?

Hypertension should be considered if the systolic blood pressure is consistently greater than the 99th percentile plus 5 mmHg for age and gestations. This varies with gestational and postnatal age, but in general is a systolic blood pressure greater than 85 mmHg in full-term infants and 60 mmHg in preterm infants.

In older infants with bronchopulmonary dysplasia (BPD) the definition is a systolic blood pressure consistently greater than 100 mmHg.

Measurement of blood pressure – Blood pressure can be measured noninvasively with oscillometric cuff devices or invasively with central or peripheral arterial catheters. If measured noninvasively, the cuff bladder should measure two-thirds the length of the extremity and one half the arm circumference. If the choice is between a cuff that is too small or one that is too large, use of the larger cuff will result in less error.

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What other disease/condition shares some of these symptoms?

In an otherwise stable neonate, stable hypertension is ordinarily idiopathic. However, coarctation of the aorta and renal artery stenosis should be considered.

What caused this disease to develop at this time?

A common form of neonatal hypertension is factitious hypertension caused by use of cuff that is too narrow for the extremity. As noted above, a cuff that is too wide will result in a small negative error; a cuff that is too narrow results in a large positive error.

Vascular Disease – Renovascular abnormalities may be congenital or associated with thrombi related to umbilical artery catheters. Such thrombi can partially or completely occlude the abdominal aorta or renal arteries, causing diminished perfusion and increased renin release. With the judicious use of catheters and the use of heparinized infusates, umbilical arterial catheter (UAC)-associated hypertension is becoming less common. Other vascular causes of neonatal hypertension include coarctation of the aorta, renal vein thrombosis, renal artery stenosis, and intrarenal microvascular changes.

Renal Parenchymal Conditions – Both congenital and acquired renal parenchymal conditions can result in neonatal hypertension. The more common congenital conditions include polycystic kidney disease and obstructive uropathy. Acquired renal diseases include acute renal failure related to shock or asphyxia and nephrocalcinosis.

Bronchopulmonary Dysplasia – Bronchopulmonary dysplasia is today one of the more common associations with neonatal hypertension with an incidence ranging from 5 to greater than 40%. The precise etiology is unknown but likely includes catecholamine excess and decreased pulmonary clearance, up-regulation or excess of angiotensin-converting enzyme, exposure to systemic steroids, and altered systemic vascular tone.

Iatrogenic Causes – Iatrogenic causes include fluid overload and with certain medications, including caffeine, systemic steroids and topical mydriatic agents.

Endocrine Causes- Endocrine causes include hyperthyroidism, mineralocorticoid excess and congenital adrenal hyperplasia.

Other Causes- Other causes or associations with neonatal hypertension include renal tumors such as mesoblastic nephromas, neuroblastomas and teratomas. Systemic hypertension can be of neurogenic origin with increased intracranial pressure most commonly related to hydrocephalus or intracranial hemorrhage. Transient hypertension may occur during seizures. A video electroencephalogram may be necessary to establish the diagnosis. Systemic hypertension has been seen in up to one-third of neonates with abdominal wall defects. Intermittent, hypertension can be seen with postoperative pain and during endotracheal intubation or suctioning.

Physical examination is stable infants is usually silent unless upper and lower extremity pulse and blood pressure discrepancies indicate coarctation of the aorta. Examination of the anterior fontanel and palpation for abdominal masses is also important.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

1. Creatinine and Blood Urea Nitrogen (BUN) indicate renal disorders, although with unilateral and even bilateral renal artery stenosis, renal function is usually normal.

2. Serum electrolyte and calcium concentrations.

3. Urinalysis, especially looking for blood and protein indicative of renal injury.

4. Thryoid studies are usually obtained for other reasons. More specific thyroid and other endocrine studies are rarely performed except with the advice of an endocrinologist.

Would imaging studies be helpful? If so, which ones?

The easiest and most relevant imaging is renal ultrasound with Doppler, looking for urinary tract anomalies, nephrocalcinosis, renovascular abnormalties, renal arterial or venous occlusion and elevated resistive indices.

If you are able to confirm that the patient has hypertension, what treatment should be initiated?

Treatment should be initiated for sustained systolic hypertension above 85 mmHg in the full-term infant, 60 mmHg in the preterm, and greater than 100 mmHg in former preterm infants with bronchopulmonary dysplasia. Treatment may be as simple as managing salt and water overload, discontinuing corticosteroids or use of a diuretic. More difficult-to-control hypertension will require antihypertensive drugs. Most neonatal systemic hypertension will come under control within a few days and resolve by 2 to 5 years of life.

In an acute hypertensive crisis a nitroprusside infusion can be easily titrated because of its short half-life and is unlikely to result in myocardial depression. For more chronic hypertension the most common class of drugs is angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. ACE inhibitors include captopril as an enteral preparation and enalapril as the parenteral form. Calcium channel blockers include amlodipine and nicardipine. Beta blockers are generally avoided because of myocardial depression and possible bronchoconstriction in bronchopulmonary dysplasia.

Antihypertensive Medications:

1) Amlodipine (p.o.) Start with 0.1 mg/kg/dose q 12 and titrate up

2) Captopril (p.o.) 0.1 – 0.5 mg/kg/dose q 8 hours. Some nephrologists employ higher doses until control is achieved.

3) Enalaprilat (IV) 10-20 mg/kg/dose q 8 hours

4) Nicardipine (IV) Start with 0.5 mg/kg/min and titrate up

5) Nitroprusside (IV) Start at 0.5 mg/kg/min and titrate

What are the adverse effects associated with each treatment option?

Complications of treatment may include fluid and electrolyte abnormalities as well as overcorrection of hypertension with hypotension.

What are the possible outcomes of hypertension?

Most neonatal systemic hypertension will come under control within a few days and resolve by 2 to 5 years of life.

What causes this disease and how frequent is it?

Hypertension is detected in less than 1% of preterm Neonatal Intensive Care Unit (NICU) patients, but in greater than 40% of older patients with bronchopulmonary dysplasia.

How do these pathogens/genes/exposures cause the disease?

The cause of idiopathic hypertension is children with bronchopulmonary dysplasia is unknown. Causes of hypertension with renal and endocrine disease vary with the disorder.

What complications might you expect from the disease or treatment of the disease?

Complications of poorly controlled hypertension include myocardial strain and hypertrophy. Acute, severe hypertension, for example from hyperthyroidism, may result in congestive heart failure.

Complications of treatment may include fluid and electrolyte abnormalities as well as overcorrection of hypertension with hypotension.

Are additional laboratory studies available; even some that are not widely available?


How can hypertension be prevented?

Hypertension associated with specific renal, cardiac, neurologic and endocrine abnormalities is part of the disease entity; prevention is usually impossible. The striking association of hypertension with bronchopulmonary dysplasia can be avoided only by prevention of that disorder.

Hypertension associated with caffeine, corticosteroroids and cardiotonic agents can be prevented by minimizing exposure to the drugs.

What is the evidence?

Lum, LG, Jones, MD. “The effect of cuff width on systolic blood pressure measurements in neonates”. J Pediatr. vol. 91. 1977. pp. 963-66.

Kent, AL, Kecskes, Z, Shadbolt, B, Falk, MC. “Normative blood pressure data in the early neonatal period”. Pediatr Nephrol. vol. 22. 2007. pp. 1335-1341. The most important step in management of neonatal hypertension is accurate measurement of blood pressure and use of reference data to establish the diagnosis:

Flynn, JT. “Neonatal hypertension: diagnosis and management”. Pediatric Nephrology. vol. 14. 2000. pp. 332-341. (This is an excellent general reference.)

Alagappan, A, Malloy, MH. “Systemic hypertension in very low birth weight infants with bronchopulmonary dysplasia: incidence and risk factors”. Am J Perinatol. vol. 15. 1998. pp. 3-8. (This article describes hypertension in 73 very low birth weight infants with and without bronchopulmonary dysplasia.)

Seliem, WA, Falk, MC, Shadbolt, B, Kent, AL. “Antenatal and postnatal risk factors for neonatal hypertension and infant follow up”. Pediatr Nephrol. vol. 22. 2007. pp. 2081-2087. (This article describes risk factors in 34 infants with hypertension. Some had elevated levels of renin and aldosterone that had decreased into the normal range in most infants by 6 months of age.)

Ongoing controversies regarding etiology, diagnosis, treatment

Since the precise pathogenesis of neonatal hypertension is largely unknown, treatment strategies will remain empiric using drugs studied in adults, but seldom in children and rarely in neonates.