KEY POINTS

• 1.
  

  Blood pressure should be measured with the proper cuff size on the right upper arm with attention to technique when using oscillometric devices in neonates.

  
  
• 2.
  

  Blood pressure is rapidly changing during the first weeks of life, especially in premature neonates, and measured values need to be compared with appropriate normal values.

  
  
• 3.
  

  In premature infants, the most common causes of hypertension are related to complications of prematurity or iatrogenic causes, whereas in term infants hypertension is most often due to an underlying condition.

  
  
• 4.
  

  A cause or risk factor for neonatal hypertension can be determined in most infants after review of the perinatal and postnatal history, physical examination, and some basic investigations.

  
  
• 5.
  

  Antihypertensive medications should be used judiciously in hypertensive neonates, given the lack of good evidence on efficacy and safety in this population.

  
  
• 6.
  

  Most prematurity-related neonatal hypertension will resolve during the first years of life, but premature and intrauterine growth restricted infants are at risk of kidney and cardiovascular disease later in life.

Introduction

Neonatal hypertension is far less common than is neonatal hypotension, and because of its infrequency, clinicians are less used to identifying and managing high blood pressures in neonates. Left unrecognized, neonatal hypertension could lead to serious cardiac, vascular, and neurologic consequences. Part of the difficulty in diagnosing high blood pressure likely comes from the fact that newborn blood pressures are naturally rapidly changing during the first weeks of life, especially in premature infants. In addition, blood pressure values by routine nursing care can be variable if not done with a proper blood pressure measurement technique.

Fortunately, when neonatal hypertension is properly identified, an underlying risk factor or cause for the hypertension is often found. A review of the perinatal and postnatal history, examination of the infant, and some basic investigations can often reveal the etiology. Although antihypertensive medications are not approved for use in this population, clinicians have been treating infants with a variety of antihypertensive medications for decades. Fortunately, most neonatal hypertension will resolve during the first months and years of life if a chronic condition is not identified. In this chapter we will describe the best evidence-based recommendations for blood pressure measurement and norms and for the diagnosis, evaluation, and management of neonatal hypertension.

Proper Blood Pressure Measurement

Although intraarterial blood pressure measurement remains the gold-standard technique and most common method in critically ill neonates, oscillometric devices are used more commonly for the majority of neonates within a neonatal intensive care unit (NICU). The evidence supporting oscillometric devices for blood pressure measurement in neonates and infants is conflicting, yet the potential for measurement error with oscillometric devices needs to be balanced against the risks of invasive monitoring with intraarterial catheters.

Intraarterial measurement of blood pressure should be used in critically ill and unstable neonates and strongly considered in those whose mean arterial pressure is <30 mm Hg. Lalan and Blowey evaluated almost 1500 paired intraarterial and oscillometric measurements in 101 ill neonates and found that oscillometric measurements overestimated radial arterial values by 4 to 8 mm Hg. Compared with umbilical arterial values, oscillometric mean values were similar for the mean arterial pressure (MAP), higher for systolic pressures, and lower for diastolic pressures, although the standard deviations of the measurements were large and clinically significant at approximately 10 mm Hg. Troy et al. also found differences in blood pressures of extremely low birth weight neonates of 10 to 18 mm Hg between intraarterial and oscillometric methods, which represented a blood pressure percent difference of 39% to 43%. Several other studies have similar findings, and although a few found good correlation between the two measurement methods, ^, there was often a large standard deviation of measured values. In addition, several studies have shown that the oscillometric method does not correlate well with intraarterial values at a lower range of blood pressures, and in particular, when the MAP is <30 mm Hg. In this setting, the oscillometric device may underestimate hypotension. A systemic review of neonatal blood pressure studies has shown that oscillometric MAP correlated best with intraarterial values, compared with systolic or diastolic blood pressure. The MAP is the only blood pressure value measured by the oscillometric device, whereas a computational algorithm determines systolic and diastolic values. Therefore, MAP should be the primary blood pressure value compared with normative data, because it is the most accurate parameter.

Blood pressures should be measured in the right upper arm using a proper cuff size with a cuff width approximately 50% of the infant arm circumference. Several early studies assessed the effect of cuff size on accuracy of blood pressure values with recommendations for using a cuff-width-to-arm-circumference ratio of 0.44 to 0.55, 0.45 to 0.70, and 0.36 to 0.64. Lum and Jones stated a rule of cuff width of 50% of the arm circumference was a reasonable estimate for proper cuff size, and this recommendation has also been endorsed by the International Neonatal Consortium after systematic evaluation of the literature. ^, Studies that have compared calf blood pressure measurements to upper arm measurements have found the calf values are more variable and the blood pressure differences between locations increases with increasing postnatal age. ^, Crapanzano et al. found that calf blood pressure was slightly less than arm values in young infants but that by 6 to 9 months of age the calf pressures exceeded arm values. In addition, the right upper arm is the preferred location for measurement in case of coarctation of the aorta.

Blood pressures should be measured in neonates and infants using a standardized blood pressure measurement technique. Several studies have shown that blood pressure values are more variable with “routine nursing care.” ^{, ,} Infant pressures may vary significantly based on state of arousal, position, sucking, and feeding. ^, Nwankwo et al. compared blood pressure values in low birth weight infants using routine nursing care with a measurement protocol and found blood pressures were significantly higher and more variable by routine care. In addition, first readings were higher than third readings in their protocol, which included three readings at 2-minute intervals for each measurement period ( Table 60.1 ). Because many factors may affect blood pressure readings, using a standard blood pressure measurement protocol should improve the accuracy of the measurements.

Physiology of Blood Pressure in Neonates

Blood pressure values at birth can be affected by maternal, perinatal, and infant factors. Maternal factors may include maternal blood pressure, diabetes, and obesity, whereas perinatal factors may include antenatal steroids, complications of pregnancy, and mode of delivery. In premature infants, the blood pressure on day 1 of life is primarily determined by the gestational age at birth and birth weight. Both Pejovic et al. and Zubrow et al. have shown a linear correlation of blood pressure on day 1 of life with birth weight and gestational age, with the most premature and lowest weight neonates having the lowest blood pressures at birth ( Fig. 60.1 ). Although other factors may play a minor role, gestational age and birth weight are consistently the strongest determinants of neonatal blood pressure on day 1 of life.

Neonatal Blood Pressure on Day 1 of Life by (1) Birth Weight and (2) Gestational Age .

(A) Systolic, (B) diastolic, and (C) mean blood pressure (MBP). (Reproduced with permission from Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in noncritically ill preterm and full-term neonates. Pediatr Nephrol . 2007;22:249–257.)

In premature infants, blood pressure rapidly changes during the first weeks of life. In fact, Pejovic et al. found that in infants born at less than 28 weeks’ gestational age, the MAP increases by 26% in the first week and >50% during the first month of life. They found the most rapid rate of increase in the most premature infants. Kent et al. determined that the phase of most rapid increase in blood pressure occurred during the first 2 to 3 weeks of life in infants born at less than 32 weeks’ gestation and only during the first week of life in infants born at 32 to 36 weeks’ gestation ( Fig. 60.2 ). They noted that the blood pressure after the rapidly increasing phase is similar to that of term infants at birth. For most term infants, blood pressure increases significantly from the first to second day of life but only modestly each day afterward. Lurbe et al. found that term infants born small for gestational age also had a lower blood pressure at birth compared with those born appropriate for gestational age but then had a rapid increase in their blood pressure during the first month of life to reach values similar to those of other neonates. These various patterns of blood pressure changes during the first months of life are illustrated in Fig. 60.3 .

Blood Pressure by Gestational Age Group During the First Weeks of Life .

Bars represent the 10th to 90th percentile blood pressures for diastolic (green) , mean (red) , and systolic (blue) blood pressure. (Reproduced with permission from Kent AL, Meskell S, Falk MC, Shadbolt B. Normative blood pressure data in nonventilated premature neonates from 28 to 36 weeks gestation. Pediatr Nephrol . 2009;24:141–146.)

Blood Pressure Patterns During the First Months of Life for Infants Born Term, Premature, Extremely Premature, and Small for Gestational Age (SGA) .

(Reproduced with permission from Dionne JM. Neonatal and infant hypertension. In: Flynn JT, Ingelfinger JR, Redwine K, eds. Pediatric Hypertension. 4th ed. New York, NY: Springer International Publishing; 2018:1–26.)

After the initial rapid rise in blood pressure, premature infants settle into a phase of slower, steadily increasing blood pressure. Zubrow et al. found that after 5 days of life, neonates increase their systolic blood pressure by about 1 mm Hg every 4 days whether born premature or term. Zubrow and the Philadelphia Neonatal Blood Pressure Study Group developed user-friendly graphs of blood pressure by postconceptional age, although unfortunately, MAP was not included. More recently, Dionne et al. synthesized blood pressure data from the literature into a reference table of infant blood pressure values after 2 weeks’ postnatal age by current postmenstrual age. The table provides the 50th, 95th, and 99th percentile values for systolic, mean, and diastolic blood pressure for infants 26 to 44 weeks postmenstrual age ( Table 60.2 ). Unfortunately, most blood pressure studies in neonates have modest patient numbers and use heterogeneous populations and measurement methods, so a large multicenter prospective study of neonatal blood pressure is greatly needed.

Incidence of Hypertension

The incidence of neonatal and infant hypertension is about 1% to 2% in the NICU and has been stable over time. In 1978 Adelman published a report on neonatal hypertension, citing an incidence of 2.5% in a single NICU and describing risk factors including umbilical artery catheters, patent ductus arteriosus, and congenital heart disease. In 1992, Singh et al. found an incidence of hypertension of 0.8% in their NICU population with risk factors that included umbilical artery catheters, chronic lung disease, patent ductus arteriosus, and intraventricular hemorrhage. A recent study of a national database by Blowey et al. found an overall NICU incidence of hypertension of 1% after exclusion of congenital heart disease. Risk factors for hypertension in this study included higher severity of illness, expiry prior to discharge, extracorporeal membrane oxygenation (ECMO), kidney failure or kidney disorder, and lower birth weight. Sahu et al. also noted a similar incidence of 1.3% hypertension in their NICU population, noting that 74% of affected infants were preterm. They also found that the term infants presented earlier, at an average of 38 days compared with 121 days in infants born at less than 28 weeks’ gestation. The actual definition of hypertension did vary in some of the early studies, but currently the most accepted definition of hypertension is a blood pressure that is consistently greater than the 95th percentile based on postmenstrual age.

One exception to the above studies is data from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, which confirmed an incidence of diagnosed hypertension of 1.8% but also found that another 3.7% of neonates had undiagnosed hypertension based on recorded blood pressure values. Of note, the AWAKEN authors used an internally generated table of normative blood pressure values, not the previously published data in Table 60.2 . Further study is needed to determine whether the higher incidence of hypertension in AWAKEN was seen because of the normative data used or whether neonatal hypertension is truly underdiagnosed.

Etiology of Hypertension

The causes of hypertension in neonates and infants are most commonly related to kidney or cardiac abnormalities, renovascular anomalies, iatrogenic causes, and/or prematurity. A summary of the common and uncommon causes of hypertension are provided in Table 60.3 . Depending on the study population, kidney causes account for 25% to 50% of infant hypertension, renovascular causes for 15% to 25%, cardiovascular causes for 4% to 8%, neurologic causes for 9% to 15%, and medications for 8% to 9%. ^, Because the hypertension associated with chronic lung disease usually develops after several months of life and even after hospital discharge, the incidence is more difficult to determine because many studies are of short duration. In analyses that included longer follow-up and/or multiple predisposing factors for the hypertension, chronic lung disease accounted for as much as 60% of infant hypertension in these studies. ^,

Table 60.3

Common and Uncommon Causes of Neonatal and Infant Hypertension

Common	Uncommon
Renovascular Renal artery thrombosis Renal artery stenosis Renal vein thrombosis	Renovascular Midaortic syndrome Congenital rubella syndrome Idiopathic arterial calcification of infancy Renal myofibromatosis
Renal parenchymal Congenital Dysplasia Unilateral hypoplasia Polycystic kidney disease	Renal parenchymal Congenital Multicystic dysplastic kidney Congenital and infantile nephrotic syndrome Renal tubular dysgenesis Atypical hemolytic uremic syndrome
Associated with urologic abnormality Obstructive uropathy Ureteropelvic junction obstruction	Associated with urologic abnormality Neurogenic bladder Megaureter
Acquired Acute tubular necrosis Cortical necrosis	Acquired Pyelonephritis Interstitial nephritis Nephrocalcinosis
Cardiovascular Coarctation of the aorta Patent ductus arteriosus ECMO	Cardiovascular Congenital ductus arteriosus aneurysm Congenital aortic aneurysm
Respiratory Chronic lung disease	Respiratory Pneumothorax
Neurologic Pain Seizures Intracranial hypertension	Neurologic Familial dysautonomia Subdural hematoma
Medications/drugs Corticosteroids Adrenergic agents Caffeine Theophylline Excess salt/saline	Medications/drugs Phthalates Phenylephrine Erythropoietin Pancuronium Vitamin D intoxication Maternal cocaine or heroin
	Endocrine Congenital adrenal hyperplasia Cushing syndrome Neonatal hyperthyroidism Hyperaldosteronism Pheochromocytoma Aldosterone synthase deficiency Argininosuccinate lyase deficiency
	Neoplastic Neuroblastoma Wilms tumor Mesoblastic nephroma Adrenocortical carcinoma
	Heritable hypertension Liddle syndrome Apparent mineralocorticoid excess Glucocorticoid-remediable aldosteronism
	Other causes Hypercalcemia Total parenteral nutrition Closure of abdominal wall defect Adrenal hemorrhage Traction

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