Advances in the ability to identify, evaluate, and care for infants with hypertension, 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). This article provides an overview of the differential diagnosis of hypertension in the neonate, the optimal diagnostic evaluation of the disease, and immediate and long-term antihypertensive therapy. (See Presentation, DDx, Workup, Treatment, and Medication.)
Blood pressure (BP) in newborns depends on various factors, including gestational age, postnatal age, and birth weight. Hypertension can be observed in various 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. (See Etiology, Presentation, and Workup.)
Etiology and Risk Factors
As in older infants and children, most cases of neonatal hypertension are of renal origin, with the 2 largest categories being renovascular and renal parenchymal diseases. Other predisposing factors include a history of umbilical catheterization and cardiac, endocrine, and pulmonary causes.
A 1992 study by Singh and colleagues clearly demonstrated that 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 in their series who had indwelling umbilical arterial catheters developed hypertension. 
The complexity of the infant’s nursery course also appears to be important in the development of hypertension. Freidman et al studied hypertension in NICU graduates and reported that infants who developed hypertension tended to have lower initial Apgar scores and slightly longer NICU stays than did infants who remained normotensive, indicating that sicker babies have a somewhat greater likelihood of developing hypertension. 
A study by Blowey et al of 764 neonates diagnosed with hypertension indicated that the greatest hypertension risk was a high severity of illness as reflected in the APR-DRG (All Patient Refined Diagnosis Related Groups) scoring system. Extracorporeal membrane oxygenation, coexisting renal disease, and renal failure also posed high risks. (Infants with congenital cardiac disorders were excluded from the study.) 
Umbilical artery catheter–associated thromboembolism
With respect to renovascular disease, umbilical artery catheter–associated thromboembolism affecting the aorta, the renal arteries, or both probably is the most common cause of hypertension 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 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.
Additional renovascular causes
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 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 1 or both renal arteries by tumors, hydronephrotic kidneys, or other abdominal masses may also lead to hypertension.
Renal parenchymal conditions
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 congestive heart failure (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-aldosterone system (RAAS) may be involved.
Additional 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.
Bronchopulmonary dysplasia (BPD)
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. For example, Alagappan found that hypertension was twice as common in very low birth-weight infants with BPD compared with the incidence in all very low birth-weight 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 reinforced the impression that infants with severe lung disease are clearly at increased risk of developing hypertension and need close monitoring for this problem.
Additional causes of hypertension
Numerous other causes of hypertension in newborns are recognized. 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 with delayed repair, which may be followed by persistent hypertension.
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.
Occurrence in the 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%. In a recent study, hypertension requiring treatment was found in 1.3% of neonates admitted to a teaching hospital NICU.  Hypertension is so unusual in otherwise healthy term infants that routine blood pressure (BP) determination is not advocated for these patients.
Hypertension may also be detected following discharge from the NICU. 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. Although the number of babies affected is likely to be relatively small, this study supports screening for hypertension in the follow-up for NICU graduates, especially those with more complicated NICU courses.
A study of approximately 2600 infants treated at a single center in Australia over a 4-year period demonstrated a prevalence of hypertension of 1.3%.  Antenatal steroids, maternal hypertension, umbilical arterial catheter placement, postnatal acute renal failure, patent ductus arteriosus, treatment with indomethacin, and chronic lung disease were associated with the development of hypertension.
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 blood pressure (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 provider is inexperienced in managing hypertension.
Other forms of neonatal hypertension may persist beyond infancy. In particular, polycystic kidney disease (PKD) and other forms of renal parenchymal disease may continue to cause hypertension throughout childhood. Infants with renal venous thrombosis (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.
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, angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers) are also unknown. Infants with neonatal hypertension 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.
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 blood pressure (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 prescribing clinician 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.
For patient education information, see High Blood Pressure (Hypertension).
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