AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Recent advances in the ability to identify, evaluate, and care for hypertensive infants, coupled with advances in the practice of neonatology in general, have led to an increased awareness of hypertension in modern neonatal intensive care units (NICUs) since its first description in the 1970s. This article discusses an overview of the differential diagnosis of hypertension in the neonate, the optimal diagnostic evaluation, and both immediate and long-term antihypertensive therapy.

Pathophysiology

Hypertension in newborn infants primarily is of renal origin, although cardiac, endocrine, and pulmonary causes have been described as well. Therefore, the pathophysiology depends on the organ system involved. For example, hypertension related to renal emboli primarily is a high renin form of hypertension, whereas the hypertension associated with bronchopulmonary dysplasia (BPD) is likely related to hypoxia. Such differences in pathophysiology are very important because they can guide the clinician with respect to evaluation and treatment.

Frequency

United States

Although precise figures are difficult to obtain, available data suggest that the incidence of hypertension in newborns is low, with published figures ranging from 0.2-3%. Hypertension is so unusual in otherwise healthy term infants that routine blood pressure (BP) determination is not advocated for these patients. In 1992, Singh and colleagues found that in a group of over 3000 infants admitted to a Chicago area NICU, the overall incidence of hypertension was found to be 0.81%. Hypertension was considerably more common in infants with BPD, patent ductus arteriosus, or intraventricular hemorrhage or in those who had indwelling umbilical arterial catheters. Approximately 9% of the infants who had indwelling umbilical arterial catheters developed hypertension.

Hypertension may also be detected following discharge from the NICU. In 1987, Friedman and Hustead diagnosed hypertension (defined as a systolic BP >113 mm Hg on 3 consecutive visits over 6 wk) in 2.6% of infants discharged from a teaching hospital NICU. The diagnosis of hypertension was made in these infants at a mean corrected age of approximately 2 months. Infants in this study who developed hypertension tended to have lower initial Apgar scores and slightly longer NICU stays than infants who remained normotensive, indicating that sicker babies have a somewhat greater likelihood of developing hypertension. Although the number of babies affected is likely to be relatively small, blood pressure screening should be included in the follow-up of NICU graduates, especially those with more complicated NICU courses.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Defining hypertension in the newborn
• • In determining the level of BP that should be considered hypertensive for a newborn infant, keep in mind that just as BP in older children has been demonstrated to increase with increasing age and body size, numerous studies have demonstrated that BP in newborns increases with both gestational and postconceptual age as well as with birthweight.
  • The most recent study demonstrating this principle is a 1995 study by Zubrow and associates, who prospectively obtained serial BP measurements from nearly 700 infants admitted to several NICUs in a large metropolitan area over a period of 3 months. They used these data to define the mean plus upper and lower 95% confidence limits for BP for the infants who were studied; their data clearly demonstrated increases in BP with increasing gestational age, birthweight, and postconceptual age. Based on these data, an infant's BP can be considered elevated if it falls above the upper limit of the 95% confidence interval for infants of similar gestational or postconceptual age and size. The curves generated by Zubrow's study have been widely published and should be consulted in assessing whether a newborn has hypertension.
  • For older infants found to be hypertensive following discharge from the nursery, the percentile curves generated by the Second Task Force on Blood Pressure Control in Childhood appear to be the most useful. These curves, which can be found in many reference texts and handbooks, allow BP to be characterized as normal or elevated not only by age and sex but also by size, albeit to a somewhat limited extent. Hypertension in this age group is defined as persistent BP elevation higher than the 95th percentile for infants of similar age, size, and sex.
• Clinical presentation: In most newborns, hypertension is discovered on routine monitoring of vital signs. Other presentations of neonatal hypertension to be aware of in acutely ill infants include congestive heart failure (CHF) and cardiogenic shock, which are potentially life threatening. Fortunately, these consequences of hypertension gradually resolve with appropriate BP reduction. In the less acutely ill infant, feeding difficulties, unexplained tachypnea, apnea, lethargy, irritability, or seizures may constitute symptoms of unsuspected hypertension. In older infants who have been discharged from the nursery, unexplained irritability or failure to thrive may be the only manifestations of hypertension.
• Patient history: Focus the history on discovering any pertinent prenatal exposures, as well as to the particulars of the infant's nursery course and any concurrent conditions. Review the procedures that the infant has undergone, especially umbilical catheter placement, and analyze the baby's current medication list. If the infant has been discharged from the nursery, the history should also cover symptoms related to possible underlying causes of hypertension.

Physical

Issues pertinent to the physical examination in neonates with hypertension can be divided into two categories, the first being proper blood pressure measurement, and the second being other components of the physical examination.

• Blood pressure measurement
• • Proper identification of hypertension in the newborn requires accurate 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. 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 monitoring BP trends over time. BP readings obtained using such devices also are useful for infants who require BP monitoring after discharge from the NICU. 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 are typically 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.
• Physical examination: The physical examination should begin with 4-extremity BP measurements in order to rule out aortic coarctation. Assess the general appearance of the infant and pay particular attention to the presence of dysmorphic features that may indicate an underlying genetic syndrome. Perform careful cardiac and abdominal examinations to rule out CHF or renal anomalies. Examine the genitalia to rule out congenital adrenal hyperplasia (CAH).

Causes

As in older infants and children, most cases of neonatal hypertension are of renal origin, with the 2 largest categories being renovascular and other renal parenchymal diseases (see Differentials).

• With respect to renovascular disease, umbilical artery catheter–associated thromboembolism affecting the aorta, the renal arteries, or both probably is the most common cause observed in the typical NICU. In 1972, Neal et al were the first investigators to demonstrate an association between the use of umbilical arterial catheters and development of arterial thrombi. Using aortography at the time of umbilical artery removal as well as autopsy data, they demonstrated thrombus formation in 25 out of 31 infants studied (81%).
• Following Neal's report, the association between umbilical arterial catheter–associated thrombi and the development of hypertension was confirmed by several other groups of investigators. Although potential predisposing factors such as duration of line placement and line position (low versus high) have been studied, these studies have not been conclusive, leading to the assumption that the cause of hypertension in such cases is related to thrombus formation at the time of line placement, which is probably related to disruption of the vascular endothelium of the umbilical artery. Such thrombi may then embolize into the kidneys, causing areas of infarction and increased renin release.
• Other renovascular problems that may lead to neonatal hypertension include renal venous thrombosis (RVT) and renal artery stenosis secondary to fibromuscular dysplasia (FMD). Many infants with FMD may have main renal arteries that appear fairly normal on angiography but demonstrate significant branch vessel disease that can cause severe hypertension.
• Other vascular abnormalities may also lead to hypertension in the newborn, including idiopathic arterial calcification and renal artery stenosis secondary to congenital rubella infection.
• Finally, mechanical compression of one or both renal arteries by tumors, hydronephrotic kidneys, or other abdominal masses may also lead to hypertension.
• Numerous congenital renal parenchymal abnormalities can lead to hypertension in the newborn period. For example, patients with autosomal dominant or autosomal recessive polycystic kidney disease (PKD) may present in the newborn period with severe nephromegaly and hypertension. The most severely affected infants with PKD are at risk for development of CHF due to severe malignant hypertension. Although much less common than in PKD, hypertension has also been reported in infants with unilateral multicystic dysplastic kidneys. Renal obstruction may be accompanied by hypertension, even in the absence of renal arterial compression. This has been observed, for example, in infants with congenital ureteropelvic junction obstruction and in infants with ureteral obstruction by other intra-abdominal masses. The mechanism of hypertension in such instances is unclear, although the renin-angiotensin system (RAS) may be involved.
• Other renal parenchymal causes of hypertension in the newborn period include severe acute tubular necrosis, interstitial nephritis, and cortical necrosis. Hemolytic uremic syndrome, although rare in the newborn period, is usually accompanied by hypertension that can be quite difficult to control, frequently requiring multiple agents.
• The most important nonrenal cause of neonatal hypertension is BPD. This association was first described in 1984 by Abman et al, who studied 65 infants discharged from a NICU. Abman et al reported that the incidence of hypertension in infants with BPD was 43% versus an incidence of 4.5% in infants without BPD. More than half of the infants with BPD who developed hypertension did not manifest it until following discharge from the NICU, highlighting the need for measurement of BP in NICU graduates. Investigators were unable to identify a clear cause of hypertension, but postulated that hypoxemia may be involved.
• These findings have subsequently been reproduced by several other investigators, most recently in 1998 by Alagappan, who found that hypertension was twice as common in very low birthweight infants with BPD compared to the incidence in all very low birthweight infants. As in Abman's report, the development of hypertension appeared to be correlated with the severity of pulmonary disease because all of the hypertensive infants were receiving supplemental oxygen and aminophylline. These observations reinforce the impression that infants with severe lung disease are clearly at increased risk of developing hypertension and need close monitoring for this problem.
• Numerous other causes of hypertension in newborns exist, a comprehensive listing of which can be found in Differentials. Of these, hypertension associated with coarctation of the thoracic aorta deserves further comment. This is perhaps one of the most easily detected forms of hypertension in the newborn period and has been included in the differential diagnosis of this problem since the earliest reported case series of neonatal hypertension.
• Repair early in infancy seems to lead to an improved long-term outcome compared to delayed repair, which may be followed by persistent hypertension. Endocrinologic disorders that may produce hypertension in the newborn period include CAH, hyperaldosteronism, and hyperthyroidism.
• Iatrogenic hypertension can be the result of medications administered to infants for treatment of pulmonary disease, such as dexamethasone and aminophylline, high doses of adrenergic agents, prolonged use of pancuronium, or administration of phenylephrine ophthalmic drops. Hypertension in such cases typically resolves when the offending agent is discontinued or its dose is reduced.
• For infants receiving prolonged total parenteral nutrition (TPN), hypertension may result from salt and water overload or from hypercalcemia. Patients with certain tumors, including neuroblastoma, Wilms tumor, and mesoblastic nephroma, may present in the neonatal period, and the tumors may produce hypertension either because of compression of the renal vessels or ureters or because of production of vasoactive substances such as catecholamines. Neurologic problems, such as seizures, intracranial hypertension, and pain, constitute fairly common causes of episodic hypertension. Finally, illicit substances ingested by the mother during pregnancy, most notably cocaine and heroin, may also lead to significant problems with hypertension in the newborn either because of direct effects on the developing kidney or because of drug withdrawal.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Renovascular conditions

Thromboembolism
Renal artery stenosis
Midabdominal aortic coarctation
Renal venous thrombosis
Compression of renal artery
Idiopathic arterial calcification
Congenital rubella syndrome

Renal parenchymal disease

Polycystic kidney disease
Multicystic-dysplastic kidney disease
Tuberous sclerosis
Ureteropelvic junction obstruction
Acute tubular necrosis
Cortical necrosis
Interstitial nephritis
Hemolytic-uremic syndrome

Pulmonary conditions

BPD
Pneumothorax

Cardiac conditions

Thoracic aortic coarctation

Endocrine conditions

Congenital adrenal hyperplasia
Hyperaldosteronism
Hyperthyroidism
Pseudohypoaldosteronism type II

Medications/Intoxications

Dexamethasone
Adrenergic agents
Vitamin D intoxication
Theophylline
Caffeine
Pancuronium
Phenylephrine
Maternal cocaine or heroin use

Tumors

Neoplasia
Wilms tumor
Mesoblastic nephroma
Neuroblastoma
Pheochromocytoma

Neurologic conditions

Pain
Intracranial hypertension
Seizures
Familial dysautonomia
Subdural hematoma

Miscellaneous conditions

Closure of abdominal wall defect
Adrenal hemorrhage
Hypercalcemia
Traction
Extracorporeal membrane oxygenation (ECMO)
Birth asphyxia
Urological neoplasms

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Usually only a limited set of laboratory data is needed in the evaluation of neonatal hypertension. Obtain serum electrolytes, creatinine, BUN, and a urinalysis in order to look for renal parenchymal disease. Obtain endocrinologic studies, such as cortisol, aldosterone, or thyroxine, when pertinent history exists.
• Measurement of plasma renin activity (PRA) is usually recommended as part of the laboratory assessment in hypertensive newborns, 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. Furthermore, many laboratories have switched from measurement of PRA to the direct renin assay, which is easier to perform. However, normative values for the direct renin assay in neonates are not widely available. Keep these factors in mind when interpreting renin values.

Imaging Studies

• Chest radiography may be helpful in infants with CHF or in those with a murmur on physical examination.
• Obtain renal ultrasonography in all hypertensive infants. Accurate renal ultrasonography may help uncover potentially correctable causes of hypertension (eg, RVT); it may detect aortic thrombi, renal arterial thrombi, or both; and it can reveal anatomic renal abnormalities or other congenital renal parenchymal disease. Ultrasonography is fast, noninvasive, and relatively inexpensive. Ultrasonography has largely replaced intravenous pyelography, which has little, if any, use in the routine assessment of neonatal hypertension.
• For infants with extremely severe BP elevation, angiography may be necessary. Although some investigators have used aortography via the umbilical artery catheter, a formal angiography using the traditional femoral venous 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 FMD.
• 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Numerous medications are available that may be used in the treatment of neonatal hypertension. Assess the clinical status of the infant and correct any easily correctable iatrogenic causes of hypertension (eg, infusions of inotropic agents, volume overload, pain) prior to instituting drug therapy. Next, choose an antihypertensive agent that is most appropriate for the specific clinical situation.

• Intravenous antihypertensive infusions
  • Usually, continuous intravenous infusions are the most appropriate initial therapy, especially in acutely ill infants with severe hypertension. The advantages of intravenous infusions are numerous, most importantly including the ability to quickly increase or decrease the rate of infusion to achieve the desired BP. As in patients of any age with malignant hypertension, take care to avoid too rapid a reduction in BP in order to avoid cerebral ischemia and hemorrhage; premature infants in particular are already at an increased risk because of the immaturity of their periventricular circulation. Because of the paucity of available data regarding the use of these agents in newborns, the choice of agent depends on the individual clinician's experience.
  • Currently available drugs for continuous infusion include sodium nitroprusside, labetalol, esmolol, and nicardipine (see Table 1). Nicardipine, which is a dihydropyridine calcium channel blocker, appears to have some advantages over older drugs, such as sodium nitroprusside, that may make it the drug of choice in this population. Regardless of the drug chosen, monitor BP continuously via an indwelling arterial catheter or by frequently repeated (q10-15min) cuff readings so that the rate of infusion can be titrated to achieve the desired degree of BP control. 

    Table 1. Intravenous Drugs for Severe Hypertension in Neonates

    Drug	Class	IV Dosage	Comments
    Diazoxide	Vasodilator (arteriolar)	2-5 mg/kg/dose rapid IV bolus	Slow IV injection ineffective; duration unpredictable; use with caution, may cause rapid hypotension; increases blood glucose levels
    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 0.75-5 mcg/kg/min IV constant infusion	Tachycardia is frequent adverse effect; must administer q4h when administered as IV bolus
    Labetalol	Alpha- and beta-blocker	0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion	Heart failure, 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 <2 mcg/kg/min, may use 10 mcg/kg/min for short duration (ie, <10-15 min)

• Intermittently administered intravenous antihypertensive agents: For some infants, intermittently administered intravenous agents have a role in therapy (see Table 1). Hydralazine and labetalol, in particular, may be useful in infants with mild-to-moderate hypertension who are not yet candidates for oral therapy because of GI dysfunction. Enalaprilat, the intravenous ACE inhibitor, has also been reported to be useful in the treatment of neonatal renovascular hypertension, but it should be used with great caution. Even doses at the lower end of published ranges may lead to significant prolonged hypotension and oliguric acute renal failure.
• Oral antihypertensive agents
  • Oral antihypertensive agents (see Table 2) are best reserved for infants with less severe hypertension or infants whose acute hypertension has been controlled with intravenous drugs and who are ready to be converted to long-term therapy. While captopril had once been considered by many authorities to be the oral drug of choice for neonatal hypertension, this has recently come under question because of the possibility of adverse effects on renal development, particularly in premature infants. It is probably acceptable for use in infants aged 38-40 weeks.
  • Beta-blockers may need to be avoided in long-term antihypertensive therapy in infants with BPD. In such infants, diuretics may have a beneficial effect not only in controlling BP but also in improving pulmonary function. Other drugs, which may be useful in some infants, include vasodilators, such as hydralazine and minoxidil (because it can be compounded into a stable suspension) and the calcium channel blocker isradipine, which may be superior to the older agents. Nifedipine is a poor choice for long-term therapy because of the difficulty in administering small doses and because of the rapid, profound, and short-lived drops in BP that are typically produced by this agent. 

    Table 2. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension

    Drug	Class	Oral Dosage	Comments
    Captopril	ACE inhibitor	<3 months: 0.01-0.5 mg/kg/dose tid; not to exceed 2 mg/kg/d >3 months: 0.15-0.3 mg/kg/dose tid; not to exceed 6 mg/kg/d	Monitor serum creatinine and potassium
    Clonidine	Central agonist	0.05-0.1 mg/dose bid-tid	Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
    Hydralazine	Vasodilator (arteriolar)	0.25-1 mg/kg/dose tid-qid; not to exceed 7.5 mg/kg/d	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 qid; not to exceed 0.8 mg/kg/d or 20 mg/d	Suspension may be compounded; useful for both acute and chronic hypertension
    Amlodipine	Calcium channel blocker	0.1-0.3 mg/kg/dose bid; not to exceed 0.6 mg/k/d or 20 mg/d	Less likely to cause sudden hypotension than isradipine
    Minoxidil	Vasodilator (arteriolar)	0.1-0.2 mg/kg/dose bid-tid	Most potent oral vasodilator; excellent for refractory hypertension
    Propranolol	Beta-blocker	0.5-1 mg/kg/dose tid	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 bid-tid, up to 12 mg/kg/d	Monitor heart rate; avoid in infants with BPD
    Spironolactone	Aldosterone antagonist	0.5-1.5 mg/kg/dose bid	Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
    Hydrochlorothiazide	Thiazide diuretic	2-3 mg/kg/d PO qd or divided bid	Monitor electrolytes
    Chlorothiazide	Thiazide diuretic	5-15 mg/kg/dose bid	Monitor electrolytes

• Few medications are approved for use in treating hypertension in neonates; therefore, all such use must be considered off-label.

Surgical Care

Surgery is rarely indicated for treatment of neonatal hypertension, except for specific diagnoses, such as ureteral obstruction, aortic coarctation, or certain tumors. Unilateral RVT is commonly treated with nephrectomy to avoid the need for long-term drug therapy. For infants with renal arterial stenosis, managing the infant medically may be necessary until growth is sufficient to undergo definitive repair of the vascular abnormalities. Infants with malignant hypertension secondary to PKD may require bilateral nephrectomy. Fortunately, such severely affected infants are quite rare.

Consultations

Consultation with a cardiologist may be indicated for performance of echocardiography or evaluation of CHF or both. Consultation with an interventional radiologist may also be needed in some cases for performance of renal angiography.

Diet

A low-sodium diet may assist in treatment of infants with persistent hypertension; however, because most infant formula is relatively low in sodium content, no special dietary modifications are usually necessary in the neonatal period.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Understand that most of the medications discussed in this article have not been studied specifically in newborns; however, through empiric use of these medications, a reasonable clinical experience has been accumulated. The information below has been summarized in Table 1 and Table 2; the tables also contain information on several other drugs, which are not included in this section because of space limitations.

Drug Category: Vasodilators

These agents relax blood vessels; thus, they decrease peripheral vascular resistance.

Drug Category: Calcium channel blockers

These agents block calcium channels in vascular smooth muscle, which leads to vasodilatation.

Drug Category: Beta-adrenergic blockers

These agents decrease heart rate and cardiac output.

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

These agents inhibit conversion of angiotensin I to angiotensin II.

Drug Category: Diuretic agents

These agents decrease plasma volume and promote excretion of water and electrolytes by the kidneys. They may be used as monotherapy or combination therapy to treat hypertension.

Drug Category: Central agonists

These agents decrease central adrenergic output.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Monitor BP regularly until the infant is ready for discharge from the NICU. Infants treated with ACE inhibitors or diuretics should have electrolyte levels and renal function monitored periodically until discharge.
• Arrangements for home BP monitoring should be part of the discharge plan for any infant sent home on antihypertensive therapy. The optimal device for home BP measurements in an infant is a Dinamap or similar oscillometric device. A second choice is a Doppler device: however, this only measures systolic BP and is difficult to teach parents to use. Therefore, oscillometric devices should be prescribed.

Further Outpatient Care

• Include BP measurement at all follow-up visits for infants with neonatal hypertension. In addition, monitor infants with BPD at discharge and those who had complicated NICU courses for the development of hypertension following discharge.
• At least one follow-up ultrasonogram should be obtained 6-12 months after discharge in infants with hypertension to ensure that the kidneys are growing normally.

In/Out Patient Meds

• Refer to preceding sections.

Transfer

• Occasionally, infants may need to be transferred to specialized centers for advanced diagnostic or therapeutic procedures, such as angiography or vascular surgery.

Deterrence/Prevention

• Although several studies have examined the role of placement of umbilical artery catheters (ie, low versus high lines), no definitive proof has emerged that changes in catheter placement can prevent thromboembolism and the subsequent development of hypertension.

Complications

• As mentioned above, the long-term sequelae of neonatal hypertension on renal growth, renal function, and future BP are unknown at this time. Long-term effects related to certain antihypertensive medications (eg, ACE inhibitors, calcium channel blockers) are also unknown. These infants may need to be monitored closely even after their hypertension has resolved, particularly with respect to renal growth and the redevelopment of hypertension in later childhood.

Prognosis

• The long-term prognosis for most infants with hypertension is quite good. For infants with hypertension related to an umbilical arterial catheter, the hypertension usually resolves over time. These infants may require increases in their antihypertensive medications in the first several months following discharge from the nursery as they undergo rapid growth. Following this, weaning the patient off antihypertensive therapy is usually possible by making no further dose increases as the infant continues to grow. Home BP monitoring by the parents is a crucially important component of this process. Provide proper equipment, either a Doppler or oscillometric device, for all infants discharged from the NICU on long-term antihypertensive medications. Such infants may benefit from referral to a comprehensive pediatric hypertension clinic if their primary care physicians are inexperienced in managing hypertension.
• Other forms of neonatal hypertension may persist beyond infancy. In particular, PKD and other forms of renal parenchymal disease may continue to cause hypertension throughout childhood. Infants with RVT may also remain hypertensive, and some of these children ultimately benefit from nephrectomy. Persistent or recurrent hypertension may also be observed in children who have undergone repair of renal arterial stenosis or coarctation of the aorta. Reappearance of hypertension in these situations should prompt a search for restenosis using the appropriate imaging studies.
• BP in newborns depends on a variety of factors, including gestational age, postnatal age, and birth weight. Hypertension can be observed in a variety of situations in the modern NICU and is especially common in infants who have undergone umbilical arterial catheterization. A careful diagnostic evaluation should lead to determination of the underlying cause of hypertension in most infants. Tailor treatment decisions, which may include intravenous therapy, oral therapy, or both, to the severity of the hypertension. Hypertension resolves in most infants over time, although a small number of infants may have persistent BP elevation throughout childhood.

Patient Education

• Educate the parents of infants who develop hypertension requiring drug therapy about the expected effects and side effects of their infant's antihypertensive medications. In addition, arrange home BP monitoring equipment and educate the parents in its use prior to the infant's discharge from the NICU. Parents must monitor the BP of all infants discharged on antihypertensive medications on a regular basis (ie, usually daily); parents should call the physician if the infant's BP exceeds or falls below the target range.
• Patient education information on childhood hypertension can be found at the International Pediatric Hypertension Association web site. Also, visit eMedicine's patient education article, High Blood Pressure.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose or treat neonatal hypertension (A major concern is missing an underlying cause of hypertension such as renal disease that might require specific therapy.)

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Abman SH, Warady BA, Lum GM, Koops BL. Systemic hypertension in infants with bronchopulmonary dysplasia. J Pediatr. Jun 1984;104(6):928-31. [Medline].
• Adelman RD. Long-term follow-up of neonatal renovascular hypertension. Pediatr Nephrol. Jan 1987;1(1):35-41. [Medline].
• Alagappan A, Malloy MH. Systemic hypertension in very low-birth weight infants with bronchopulmonary dysplasia: incidence and risk factors. Am J Perinatol. Jan 1998;15(1):3-8. [Medline].
• Boedy RF, Goldberg AK, Howell CG Jr, et al. Incidence of hypertension in infants on extracorporeal membrane oxygenation. J Pediatr Surg. Feb 1990;25(2):258-61. [Medline].
• Crapanzano MS, Strong WB, Newman IR, et al. Calf blood pressure: clinical implications and correlations with arm blood pressure in infants and young children. Pediatrics. Feb 1996;97(2):220-4. [Medline].
• Crossland DS, Furness JC, Abu-Harb M, et al. Variability of four limb blood pressure in normal neonates. Arch Dis Child Fetal Neonatal Ed. Jul 2004;89(4):F325-7. [Medline].
• Duley L. Pre-eclampsia and the hypertensive disorders of pregnancy. Br Med Bull. 2003;67(1):161-76. [Medline].
• Elliot SJ, Hansen TN. Neonatal hypertension. In: Long WA, ed. Fetal and Neonatal Cardiology. Philadelphia, Pa:. WB Saunders Co;1990:492-498.
• Flynn JT. Neonatal hypertension: diagnosis and management. Pediatr Nephrol. Apr 2000;14(4):332-41. [Medline].
• Flynn JT, Smoyer WE, Bunchman TE. Treatment of hypertensive children with amlodipine. Am J Hypertens. Oct 2000;13(10):1061-6. [Medline].
• Flynn JT, Warnick SJ. Isradipine treatment of hypertension in children: a single-center experience. Pediatric Nephrology. 2002;17:748-53. [Medline].
• Friedman AL, Hustead VA. Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up. Pediatr Nephrol. Jan 1987;1(1):30-4. [Medline].
• Gouyon JB, Geneste B, Semama DS, et al. Intravenous nicardipine in hypertensive preterm infants. Arch Dis Child Fetal Neonatal Ed. Mar 1997;76(2):F126-7. [Medline].
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Article Last Updated: Aug 29, 2006