Approach Considerations

Usually only a limited set of laboratory data are needed in the evaluation of neonatal hypertension. Obtain serum electrolyte, calcium, creatinine, and blood urea nitrogen (BUN) analysis, as well as urinalysis, in looking for renal parenchymal disease. Obtain endocrine studies, such as cortisol, aldosterone, or thyroxine, when pertinent history is noted.

Blood pressure measurement

Proper identification of hypertension in the newborn requires accurate blood pressure (BP) measurement. Fortunately, in most acutely ill infants, BP is usually monitored directly via an indwelling arterial catheter, either in the radial or umbilical artery. This method provides the most accurate BP readings and is clearly preferable to other methods.^[8]

In infants who do not have indwelling umbilical lines, automated oscillometric devices are an acceptable alternative method of BP measurement. Although BP readings obtained using such devices may differ slightly from intra-arterial readings, they are easy to use and facilitate the monitoring of BP trends over time. BP readings obtained using such devices are also useful for infants who require BP monitoring after discharge from the NICU. Repeat determinations are advised due to the tendency of oscillometric devices to inflate to a preset value on the first reading.

Pay attention to the size of the cuff and also to the extremity used. Most normative BP data, not only in infants but also in older children, have been collected using BP measurements obtained in the right arm. Because BP measurements obtained in the leg may be slightly higher than those obtained in the arm, the use of other extremities for routine BP determination may complicate the evaluation of hypertension. The nursing staff should document the extremity used for BP determinations and try to use the same extremity for all BP measurements, especially in infants who require antihypertensive treatment.^[24]

Imaging Studies

Chest radiography may be helpful in infants with congestive heart failure (CHF) or in those with a murmur upon physical examination.

Perform renal ultrasonography with Doppler of the renal vessels in all hypertensive infants. Accurate renal ultrasonography may help to uncover potentially correctable causes of hypertension (eg, renal venous thrombosis [RVT]), it may detect aortic thrombi and/or renal arterial thrombi, and it may reveal anatomic renal abnormalities or other congenital renal parenchymal disease. Ultrasonography is fast, noninvasive, and relatively inexpensive. The modality has largely replaced intravenous pyelography, which has little, if any, use in the routine assessment of neonatal hypertension.

For infants with extremely severe blood pressure (BP) elevation, angiography may be necessary. Although some investigators have used aortography via the umbilical artery catheter, formal renal arteriography using the traditional femoral vascular approach is much more accurate for diagnosing renal arterial stenosis, primarily because of the high incidence of intrarenal branch vessel abnormalities observed in children with fibromuscular dysplasia. Depending on the expertise available, this may need to be deferred until the infant is larger. Magnetic resonance (MR) and computed tomography (CT) angiography are of little value in infants, as they do not provide sufficient resolution to identify branch vessel stenoses.

Nuclear scanning may demonstrate abnormalities of renal perfusion caused by thromboembolic phenomenon, although obtaining good studies in infants is difficult because of their immature renal function. Obtain other studies, including echocardiography and voiding cystourethrography, as indicated.

Laboratory Studies

Most infants who present with significant hypertension will already have had the basic laboratory studies needed for the evaluation. Essential lab tests include:

Electrolytes, BUN, creatinine, calcium, and phosphorus
Urinalysis ± urine culture if indicated
Urine electrolytes, calcium, creatine as indicated
Plasma renin (see below), aldosterone, cortisol, TSH as indicated from history, physical exam and/or basic lab tests

Measurement of plasma renin activity (PRA) is usually recommended as part of the laboratory assessment in newborns with hypertension, although elevated peripheral renin levels may not signify the presence of underlying pathology, because renin values are typically high in infancy. In addition, plasma renin levels may be falsely elevated by medications that are commonly used in the NICU, such as aminophylline. Keep these factors in mind when interpreting renin values.

Alternatively, suppressed PRA in an infant with hypertension is a significant finding, possibly indicating the presence of a genetic form of hypertension associated with volume overload, such as glucocorticoid-remediable aldosteronism or Liddle Syndrome.

Treatment & Management

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Media Gallery

Neonatal Hypertension. Normal blood pressure percentile curves for older infants. From the Second (1987) Task Force on Blood Pressure Control in Childhood; National Heart, Lung, and Blood Institute.

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Table 1. Neonatal Blood Pressures and Potential Treatment Parameters. Adapted from Dionne et al.*

Postconceptual Age	50th Percentile	95th Percentile	99th Percentile
44 weeks
SBP	88	105	110
DBP	50	68	73
MAP	63	80	85
42 weeks
SBP	85	98	102
DBP	50	65	70
MAP	62	76	81
40 weeks
SBP	80	95	100
DBP	50	65	70
MAP	60	75	80
38 weeks
SBP	77	92	97
DBP	50	65	70
MAP	59	74	79
36 weeks
SBP	72	87	92
DBP	50	65	70
MAP	57	72	77
34 weeks
SBP	70	85	90
DBP	40	55	60
MAP	50	65	70
32 weeks
SBP	68	83	88
DBP	40	55	60
MAP	49	64	69
30 weeks
SBP	65	80	85
DBP	40	55	60
MAP	48	63	68
28 weeks
SBP	60	75	80
DBP	38	50	54
MAP	45	58	63
26 weeks
SBP	55	72	77
DBP	30	50	56
MAP	38	57	63

Table 2. Intravenous Drugs for Severe Hypertension in Neonates ^[21]

Drug	Class	Intravenous (IV) Dosage	Comments
Esmolol	Beta blocker	100-300 mcg/kg/min IV infusion	Very short acting; constant IV infusion necessary
Hydralazine	Vasodilator (arteriolar)	0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusion	Tachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
Labetalol	Alpha blocker and beta blocker	0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion	Heart failure, bronchopulmonary dysplasia (BPD), relative contraindications
Nicardipine	Calcium channel blocker	1-5 mcg/kg/min IV constant infusion	May cause reflex tachycardia
Sodium nitroprusside	Vasodilator (arteriolar and venous)	0.5-10 mcg/kg/min IV constant infusion	Thiocyanate toxicity can occur with prolonged use (>72 h) or in renal failure; usual maintenance dose is below 2 mcg/kg/min; may use 10 mcg/kg/min for short duration (ie, < 10-15 min)

Table 3. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension ^[21]

Drug	Class	Oral Dosage	Comments
Captopril	Angiotensin-converting enzyme (ACE) inhibitor	Under age 3 months: 0.01-0.5 mg/kg/dose 3 times daily; not to exceed 2 mg/kg/day At or above age 3 months: 0.15-0.3 mg/kg/dose 3 times daily; not to exceed 6 mg/kg/day	Monitor serum creatinine and potassium levels
Clonidine	Central agonist	0.05-0.1 mg/dose 2-3 times daily	Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
Enalapril	ACE inhibitor	0.08-0.6 mg/kg/day, given once or twice daily	Monitor serum creatinine and potassium levels
Hydralazine	Vasodilator (arteriolar)	0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/day	Suspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
Isradipine	Calcium channel blocker	0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/day	Suspension may be compounded; useful for both acute and chronic hypertension
Amlodipine	Calcium channel blocker	0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/d	Less likely to cause sudden hypotension than isradipine
Minoxidil	Vasodilator (arteriolar)	0.1-0.2 mg/kg/dose 2-3 times daily	Most potent oral vasodilator; excellent for refractory hypertension
Propranolol	Beta-blocker	0.5-1 mg/kg/dose 3 times daily	Maximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
Labetalol	Alpha and beta blocker	1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/d	Monitor heart rate; avoid in infants with BPD
Spironolactone	Aldosterone antagonist	0.5-1.5 mg/kg/dose twice daily	Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
Hydrochlorothiazide	Thiazide diuretic	2-3 mg/kg/d orally every day or divided twice daily	Monitor electrolytes
Chlorothiazide	Thiazide diuretic	5-15 mg/kg/dose twice daily	Monitor electrolytes