eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Neonatal Hypertension

Author: Joseph Flynn, MD, MS, Director of Pediatric Hypertension Program, Division of Nephrology, Children's Hospital and Regional Medical Center; Professor, Department of Pediatrics, University of Washington School of Medicine
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Updated: Dec 4, 2008

Introduction

Background

Recent 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 ICUs (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.

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%.¹ Antenatal steroids, maternal hypertension, umbilical arterial catheter, postnatal acute renal failure, patent ductus arteriosus, treatment with indomethacin, and chronic lung disease were associated with the development of 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.² 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 of NICU graduates, especially those with more complicated NICU courses.

Clinical

History

• Identifying hypertension in the newborn
  • Blood pressure in newborn infants is influenced by various factors, including birthweight, gestational age, and postconceptual age.
  • Excellent normative data illustrating the importance of these factors was generated by Zubrow et al, who prospectively obtained serial blood pressure (BP) measurements from nearly 700 infants admitted to several neonatal ICUs (NICUs) in a large metropolitan area over 3 months.³ They used these data to define the mean plus upper and lower 95% confidence limits for BP; their data clearly demonstrated increases in BP with increasing gestational age, birthweight, and postconceptual age. The Zubrow data are probably most useful in identifying hypertension in premature and term newborns. Using their data, an infant's BP is 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 the study have been widely published and should be consulted in assessing hypertension in a newborn.
  • For older infants found to be hypertensive following discharge from the nursery, the percentile curves generated by the 1987 Second Task Force on Blood Pressure Control in Childhood remain the most useful reference for infants aged 1 year or younger.⁴ 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 BP elevation ≥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: proper BP measurement and other components of the physical examination.

• BP 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 are also 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 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.
• 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). Other predisposing factors include a history of umbilical catheterization and chronic lung disease.

• A 1992 study by Singh and colleagues clearly demonstrated that hypertension was considerably more common in infants with bronchopulmonary dysplasia (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.⁵
• 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 infants who remained normotensive, indicating that sicker babies have a somewhat greater likelihood of developing hypertension.²
• 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 of 31 infants studied (81%).⁶
• 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.
• 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.
• 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.⁷ 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.⁸ 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 are recognized, 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.

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