Etiology, clinical features, and diagnosis of neonatal hypertension

INTRODUCTION — Hypertension can be detected in 1 to 2.5 percent of all neonates (both term and preterm infants) admitted to neonatal intensive care units (NICUs). The clinician needs to be knowledgeable about normative blood pressure (BP) values, the optimal method to measure BP in newborns, the underlying etiologies, and clinical manifestations to identify and treat neonatal hypertension.

The definition, etiology, clinical features, and diagnostic evaluation of neonatal hypertension will be reviewed here. Treatment of hypertension in infants is discussed separately. (See "Management of hypertension in neonates and infants".)

DEFINITION

Hypertension — The diagnosis of hypertension in neonates may be considered when there are persistent systolic and/or diastolic blood pressure (BP) values that exceed the 95^th percentile for postmenstrual (sometimes referred to as postconceptional) age (figure 1 and table 1). However, it is challenging to define normal neonatal BP as there is a lack of robust normative BP data in this age group. In addition, there are a number of factors that affect normal BP values during the neonatal period (defined as the first 28 days of life) [1]. As a result, it has been difficult to develop a standardized definition of hypertension for clinical use in this age group.

Normal blood pressure — It is challenging to establish normative values for neonatal BP, especially in preterm infants, because of the effects of gestational age and maturation on BP values. BP values increase following birth, with greater rates of increase seen in preterm infants compared with term infants [1] (see "Assessment and management of low blood pressure in extremely preterm infants", section on 'Physiological changes in BP'). In addition, the lack of large-scale, prospective, multicenter studies of neonatal BP further complicates the problem of defining normative BP data for neonates, especially preterm and ill term infants.

Nevertheless, based on a review of these data, a reference table of normal BP values at or after two weeks of age in infants between 26 and 44 weeks postconceptional age has been published (table 1) [2]. This table, which is based on the best available data through 2010, can be used clinically to identify infants with abnormal BP values that may require further evaluation and/or treatment. (See 'Evaluation' below and "Management of hypertension in neonates and infants".)

The following observations about normal neonatal BP can be concluded from the data presented below:

●The primary determinant of neonatal BP is postmenstrual age (gestational age at birth plus chronologic age).

●In neonates admitted to the neonatal intensive care unit (NICU), BP varies with gestational age, postmenstrual age, and birth weight. In all infants regardless of gestation, the rise in BP is higher during the first week of life. The rate of rise is more rapid in preterm compared with term infants.

●In healthy term infants, BP does not vary based on growth parameters or gestational age. BP does increase over the first three to four days of life but levels off sooner than what is observed in preterm infants.

Infants cared for in the NICU — Useful data on BP in newborns were obtained in a study of 608 newborns admitted to 14 NICUs in the Philadelphia area (figure 2 and figure 3) [3]. Systolic BP and diastolic BP were measured by an oscillometric device every eight hours for 1 to 99 days after delivery. The following findings were noted:

●On day 1, systolic and diastolic BP correlated strongly with birth weight and gestational age.

●During the first five days after birth, systolic BP and diastolic BP progressively rose by 2.2 to 2.7 mmHg/day and 1.6 to 2 mmHg/day, respectively, regardless of gestational age or birth weight.

●Systolic and diastolic BP continued to increase after the fifth day of age but at more gradual increments (0.24 to 0.27 mmHg/day and 0 to 0.15 mmHg/day, respectively).

●In a multiple regression analysis, the primary determinant of BP was postmenstrual (postconceptual) age (gestational plus postnatal age) (figure 1) [3].

Similar results were noted in a study of 373 hemodynamically stable infants (292 preterm and 81 term neonates) admitted to the NICU, in whom BP data were obtained utilizing an oscillometric device [4]. In this cohort, BP on day 1 of life correlated with gestational age and birth weight. In all infants regardless of gestational age, BP increased at a faster rate over the first week of life, followed by subsequent slowing. The rate of rise was more rapid in preterm infants compared with term infants [5].

In a study of 367 extremely preterm infants (gestational age between 23 and <27 weeks), arterial BP initially decreased within the first three hours of life and then spontaneously increased over the first 24 hours of life [6]. The average rise of mean BP was 0.2 mmHg per hour and did not differ between untreated infants and those who received antihypotensive therapy (eg, fluid bolus or drug therapy). Although there was a wide range of BP values, the mean systolic, diastolic, and mean BP increased with increasing gestational age similarly to observations noted in studies of more mature infants.

Infants cared for in the normal nursery — Healthy term infants cared for in the normal nursery demonstrate a somewhat different pattern from the above studies. This was illustrated in an Australian prospective study of 406 term infants with a mean gestational age of 40 weeks born between 2003 and 2005, in whom BP measurements were determined by oscillometric methods [7]. The following findings were noted:

●At 12 to 24 hours of life, median systolic, diastolic, and mean BPs were 65 (range 46 to 94), 45 (range 24 to 57), and 48 (range 31 to 63), respectively. Unlike what was seen in the studies of preterm infants, no difference in BP was seen on day 1 of life based on birth weight, length, or gestational age.

●BP measurements increased over the next four successive days by 1 to 2 mmHg/day. On days 2, 3, and 4 of life, median systolic BP measurements were 68, 69.5, and 70, respectively; median diastolic BPs were 43, 44.5, and 46, respectively; and median mean BPs were 51, 52, and 54, respectively. The differences between days 3 and 4 were not significant, suggesting an earlier leveling off of BP than that observed in preterm infants.

INCIDENCE AND RISK FACTORS — The incidence of neonatal hypertension varies depending on the clinical setting. In otherwise healthy term infants, hypertension is exceedingly uncommon, with a reported rate of 0.2 percent [8].

In infants admitted to a neonatal intensive care unit (NICU), the incidence is higher, with reported rates ranging from 0.7 to 3 percent [9-15]. Risk factors for hypertension in patients admitted to the NICU include low gestational age and birth weight, specific diseases (eg, bronchopulmonary dysplasia, cardiac disease, and acute kidney injury [AKI]), use of umbilical arterial catheters (UACs), and increasing severity of illness.

●In an analysis of data from Pediatric Health Information System of 123,847 infants discharged from NICUs between 2005 and 2009, 1.7 percent had a diagnosis of hypertension encoded at the time of discharge [13]. After patients with cardiac disease were omitted, 1 percent of patients (n = 764) were diagnosed with hypertension of the remaining 78,986 patients cared for at 36 different institutions. In a multivariate analysis of hypertensive patients without cardiac disease, risk factors for hypertension included low birth weight, kidney disease, neonatal abstinence syndrome, use of extracorporeal membrane oxygenation, and increasing severity of illness.

●In a retrospective Australian study of 2572 newborn infants born between 2001 and 2005 and admitted to the NICU, 1.3 percent of infants were diagnosed with hypertension (defined as systolic or mean blood pressure [BP] >95^th percentile for gestational age) at a median postnatal age of five days [12]. Hypertensive infants were more likely to have a lower gestational age, birth weight, and length than were normotensive infants. Other factors associated with hypertension included antenatal steroid administration, maternal hypertension, UAC use, postnatal AKI, patent ductus arteriosus, and bronchopulmonary dysplasia.

●In a retrospective single-center review of 4203 neonates admitted to the NICU from 2006 to 2009, 53 patients (1.3 percent) had persistent hypertension that was treated with antihypertensive therapy [16]. Logistic regression analysis identified bronchopulmonary dysplasia and patent ductus arteriosus as risk factors for hypertension. Other common features of hypertensive infants included use of umbilical catheters and presence of systemic diseases such as kidney disease.

●An analysis of data from the multinational, multicenter Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) noted that hypertension went unrecognized in many neonates, especially those with AKI [14]. In this study of 2162 neonates cared for in the NICU, hypertension was diagnosed in 1.8 percent, but an additional 3.7 percent of the cohort were identified has having undiagnosed hypertension.

●Hypertension is also reported after NICU discharge. In a study of 654 infants seen in a neonatal follow-up clinic, 17 (2.6 percent) were found to have hypertension (defined as systolic BP >113 mmHg by Doppler) at a mean postconceptional age of 49 weeks [11]. Compared with a control group of 212 normotensive infants, the hypertensive infants tended to have lower birth weights, lower one-minute Apgar scores, and longer lengths of stay in the NICU, but none of the differences were statistically significant.

MEASUREMENT — Comparison of an infant's blood pressure (BP) wih normative values requires proper measurement. BP can be measured invasively or noninvasively. The ideal setting to measure BP is while the infant is sleeping or resting because crying, pain, feeding, and agitation all can increase BP [17].

Intraarterial measurement — Direct intraarterial measurement through a catheter placed in the aorta or the radial artery is the most accurate technique. It also provides continuous readings. The degree to which radial pressures correlate with aortic pressures is uncertain. In adults, radial artery systolic BP measurements may be 20 to 30 percent higher than central values, although mean and diastolic measurements are comparable [18]. However, radial pressures appear to more closely mimic aortic pressures in newborns [19].

Complications associated with intraarterial catheters include thrombosis and infection. Thus, they should be used to monitor BP only when the catheter is needed for a significant clinical indication, such as frequent blood sampling, hypotension requiring pressor support, or severe hypertension requiring treatment with intravenous antihypertensives.

Noninvasive measurement — Numerous noninvasive devices are available to measure BP. The most common technique is oscillometry, which estimates the mean arterial pressure and then back-calculates the systolic and diastolic pressures. The algorithms used for these calculations vary between manufacturers, so different devices may give different BP values in the same patient. A systematic review of the literature reported that accurate oscillometry BP was dependent on proper BP techniques including cuff size (arm circumference ratio of approximately 0.5) and consistent location of BP measurement (upper arm) [20].

Cuff size — A critical component of noninvasive BP measurement is use of an appropriately sized cuff [20,21]. The cuff bladder should measure two-thirds the length of the extremity and 0.44 to 0.55 of the arm circumference (figure 4). If the choice is between a cuff that is too small or one that is too large, use of the larger cuff will result in less error. Most normal BP values are derived from upper arm measurements. Thus, BP usually is measured in an arm. In the term infant with a maximum arm circumference of 10 cm, the usual dimensions of an appropriately sized cuff bladder are 4 cm in width and 8 cm in length.

If a leg is used, an appropriately sized cuff should be selected, that is, one that is two-thirds the length of the extremity. With appropriately sized cuffs, lower and upper extremity BPs are nearly identical in the neonatal period [22]. The medical record should note the site of measurement.

Correlation with intraarterial blood pressure — Although these devices are generally felt to correlate well with intraarterial BP measurements, some studies have demonstrated notable differences [20]. A systematic review of the literature reported that BP obtained by oscillometry compared with those obtained by intraarterial measurements correlated best for mean arterial pressure [20]. However, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise than intraarterial measurements, especially in neonates with a mean arterial pressure <30 mmHg. Despite these findings, oscillometric devices are useful for BP measurement in the neonatal intensive care unit (NICU) as they allow for continuous BP monitoring and can demonstrate trends in BP. However, clinicians need to be aware of the possible overestimation of oscillometric BP versus intraarterial BP. Prior to making any clinical management decision, oscillometric BP measurements need to be confirmed based on a standard protocol, as discussed below. (See 'Our approach' below.)

Our approach — For noncritically ill infants in whom hypertension is suspected, we use the following standard protocol to measure BP [5,20]:

●BP measured by oscillometric device

●BP measurement preferentially performed 1.5 hours after a feed or medical intervention

●Infant lying in a prone or supine position

●Use of an appropriately sized BP cuff

●BP measurement performed in the right upper arm

●After cuff placement, BP should be measured several minutes after the infant has settled into a calm state

●BP measurement performed while the infant is asleep or in quiet awake state

●If an automated BP device is used, the first reading is typically discarded

ETIOLOGY — Although numerous causes have been identified, the most common causes of neonatal hypertension are umbilical arterial catheter (UAC)-associated thromboembolism, chronic lung disease, and kidney disease (table 2) [13,16]. However, sometimes, no specific underlying cause is identified. This was illustrated in a multicenter case series from the United States that reported an inability to determine the etiology in approximately 50 percent of hypertensive infants [23]. In patients with no identified cause, hypertension may be due to the presence of an undetectable renovascular event.

Vascular disease

Umbilical arterial catheter-associated thrombosis — The most common renovascular abnormality associated with neonatal hypertension is thrombosis associated with UAC placement [24-27]. Thrombi that form on the tip or surface of the catheter can partially or completely occlude the abdominal aorta, thereby decreasing kidney perfusion. These thrombi may then embolize into the renal vasculature, resulting in local areas of infarction (toes (picture 1)) and increased renin release.

Thrombi are common in newborns with UACs [24,26,27].

●In a prospective study, 18 of 19 patients had evidence of thrombus formation detected by contrast aortography [27]. In addition, there were several instances of clot fragmentation and embolization. Thrombosis was also seen at autopsy in 7 of 12 infants who had died.

●In a study using serial ultrasonography, abdominal aortic thrombi were detected in 32 of 99 consecutive patients (32 percent) after removal of a UAC [26].

●In another report, 11 of 12 newborns with hypertension had renal artery thrombosis demonstrated by radionuclide scan and/or angiography [28]. Blood pressure (BP) normalized with antihypertensive therapy and remained normal after discontinuation of treatment. At follow-up at a mean age of 5.75 years, scans remained abnormal and five patients had unilateral kidney atrophy.

The risk of UAC-associated thrombosis increases with increasing duration of UAC use, high UAC placement (ie, catheter above the diaphragm versus low placement, just above the aortic bifurcation) [29], lack of use of heparinized infusate [30], and trauma to the endothelial surface while the catheter is in situ or during catheter insertion. In addition to hypertension, other serious long-term sequelae of UAC use include coarctation of the abdominal aorta due to scarring [31] and aneurysmal dilatation [32].

Other vascular causes — Other vascular causes of neonatal hypertension include:

●Coarctation of the aorta, which may be recognized by absent or diminished femoral pulses or a differential in BP between the upper and lower extremities. However, there is considerable variability in four-extremity BPs in neonates, making it necessary to obtain an echocardiogram to definitively confirm or exclude coarctation of the aorta [33]. A rare variation is the mid-aorta syndrome, in which there is segmental narrowing of the distal thoracic aorta or abdominal aorta and stenosis of branch vessels [34,35]. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

●Renal vein thrombosis, which classically presents with the triad of a flank mass, gross hematuria, and thrombocytopenia [36]. (See "Neonatal thrombosis: Clinical features and diagnosis", section on 'Renal vein thrombosis'.)

●Renal artery stenosis is a rare cause of neonatal hypertension [37,38]. Fibromuscular dysplasia accounts for the majority of cases of renal artery stenosis in childhood, although renal artery stenosis can be seen in genetic syndromes such as neurofibromatosis and Williams syndrome. Renovascular disease is sometimes associated with congenital rubella infection [39,40]. (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Kidney disease' and "Congenital rubella", section on 'Late manifestations'.)

●Other rare vascular causes include congenital abdominal aortic aneurysm [41] and idiopathic arterial calcification [42].

Kidney disorders — Kidney diseases associated with hypertension can be separated into congenital and acquired disorders.

Congenital disorders — Congenital kidney and urologic disorders that are associated with neonatal hypertension include:

●Polycystic kidney disease (PKD) – Both autosomal recessive and autosomal dominant PKD (ARPKD and ADPKD, respectively) are frequently accompanied by hypertension. In a large series of children with ARPKD diagnosed after 1990 (median age 5.4 years), 65 percent had hypertension, which was detected at a median age of 16 days (range 5 to 165 days) [43]. ADPKD also can present in newborns, and, in these patients, hypertension, although rare, may be present. (See "Autosomal dominant polycystic kidney disease (ADPKD) in children", section on 'Kidney manifestations'.)

●Multicystic dysplastic kidney (MCDK) – In contrast, hypertension is unusual in newborns with unilateral MCDK, although some cases have been described [44]. In one case series of infants with MCDK, hypertension was reported in 5.9 percent of patients [45]. It sometimes occurs in later infancy or childhood [46]. (See "Kidney cystic diseases in children", section on 'Multicystic dysplastic kidney'.)

●Obstructive uropathy – Hypertension may accompany obstructive uropathy, such as ureteropelvic junction obstruction [47,48]. BP usually normalizes with surgical correction of the obstruction, but persistent hypertension has been described [49]. (See "Congenital ureteropelvic junction obstruction".)

Acquired kidney parenchymal diseases — Acquired kidney diseases associated with neonatal hypertension include:

●Acute kidney injury (AKI) – Approximately 10 to 20 percent of newborns with AKI have hypertension, which may go unrecognized [14]. The most common cause of AKI in newborns is acute tubular necrosis, which is usually due to perinatal asphyxia, sepsis, or other causes of inadequate renal perfusion. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis".)

●Nephrocalcinosis – Nephrocalcinosis is common in preterm infants. Affected infants rarely have hypertension, unless an obstructive calculus forms. However, infants with persistent nephrocalcinosis may develop hypertension. This was illustrated in a series of 83 of 201 preterm infants who had persistent nephrocalcinosis at term postmenstrual age [50]. Of these, systolic and diastolic BPs were >95^th percentile at one and two years of age in 39 and 48 percent and 30 and 34 percent, respectively. (See "Nephrocalcinosis in neonates".)

Bronchopulmonary dysplasia — Systemic hypertension is common in infants with bronchopulmonary dysplasia [23,51-53]. The incidence ranges from 5 to 40 percent, depending on birth weight and severity of lung disease [23,51-54].

The mechanism of hypertension in bronchopulmonary dysplasia is uncertain and may include increases in sympathetic activity and angiotensin II [54]. The association between hypertension and more severe bronchopulmonary dysplasia also suggests that hypoxemia may play a role, which may be based on a genetic predisposition [55]. (See "Bronchopulmonary dysplasia (BPD): Management and outcome", section on 'Cardiovascular complications'.)

Hypertension may not present until four to five months of age. It often is associated with the use of dexamethasone or other glucocorticoids [56-58]. If related to these drugs, it usually abates when therapy is discontinued. (See "Evaluation and diagnosis of hypertension in infants between one month and one year of age".)

Iatrogenic causes — Iatrogenic causes of neonatal hypertension include fluid overload and medications.

●Medications – Medications that can cause hypertension include glucocorticoids [56-58], pancuronium, and topical mydriatic agents [59].

●Phthalate exposure – Phthalates, including di-2-ethylhezyl phthalate (DEHP), are plasticizing agents that are commonly present in intravenous bags and tubing, as well as some endotracheal tubes and continuous positive airway pressure systems. One study suggests that phthalate exposure may be associated with "idiopathic" neonatal hypertension, which typically develops near 40 weeks postmenstrual age, has low plasma renin activity, is transient, and responds favorably to spironolactone [60]. Many infants requiring neonatal intensive care unit (NICU) care are exposed to excessive levels of phthalates, and such exposures are linearly related to BP. The proposed mechanism is activation of the mineralocorticoid receptor through inhibition of 11-beta-hydroxysteroid dehydrogenase 2. In a report from the same center, the incidence of neonatal hypertension decreased from 7.7 to 1.4 percent when DEHP was removed from intravenous fluids, then rebounded to 10.1 percent when DEHP-containing fluids were resumed [61]. These observations have not yet been independently confirmed.

Endocrine causes — Endocrine causes include hyperthyroidism [62] and mineralocorticoid excess, which, in neonates, is most often due to congenital adrenal hyperplasia [63]. Hypertension and, frequently, hypokalemia, which are due to excess deoxycorticosterone, are typically present in congenital adrenal hyperplasia due to CYP11B1 (11-beta-hydroxylase) and CYP17 (17-alpha-hydroxylase) deficiencies. In neonates, CYP11B1 deficiency also is associated with ambiguous genitalia in females (clitoral enlargement, labial fusion, formation of a urogenital sinus) and penile enlargement in males. (See "Uncommon congenital adrenal hyperplasias", section on '11-beta-hydroxylase deficiency' and "Uncommon congenital adrenal hyperplasias", section on 'CYP17A1 deficiencies'.)

Miscellaneous causes — Other reported causes of neonatal hypertension include:

●Masses in or near the kidney, including mesoblastic nephroma [64], neuroblastoma [65], and Wilms tumor [66]. (See "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma" and "Presentation, diagnosis, and staging of Wilms tumor".)

●Increased intracranial pressure from cerebral edema or intracranial hemorrhage. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis".)

●Hypertension occurs in 40 to 60 percent of patients during extracorporeal membrane oxygenation [67,68]. The underlying mechanism is unknown but is believed to be multifactorial, including fluid overload, altered renal sodium, and water handling. Development of hypertension does not appear to be related to increased plasma renin activity, sodium or colloid loads, or their rates of infusion.

●Approximately one-third to almost one-half of neonates have hypertension after closure of abdominal wall defects [69]. The mechanism is attributed to increased intraabdominal pressure causing transient changes in renal blood flow, rennin-angiotensin system, and urine flow, as well as increased catecholamine secretion. The hypertension is usually transient and does not require any antihypertensive medication [70].

●Postoperative or procedural pain (eg, endotracheal intubation [71] or suctioning [72,73]). (See "Assessment of pain in neonates".)

●Maternal cocaine and heroin use have been reported to cause persistent neonatal hypertension [74]. Withdrawal from long-term use of sedative and/or analgesics may also be associated with hypertension. (See "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Clinical features and diagnosis".)

●For infants receiving prolonged parenteral nutrition, hypertension may result from salt and water overload or from hypercalcemia caused either directly by excessive calcium intake or indirectly by vitamin A or D intoxication.

●Genetic variants, including the presence of the CC genotype of CYP2D6 [55] or biallelic loss of function of NPR1 have been demonstrated in some neonates with elevated BP [75].

CLINICAL FEATURES — Most hypertensive newborns are asymptomatic, and the diagnosis is made by routine blood pressure (BP) measurement. In patients with signs or symptoms, the magnitude of hypertension may not correlate with its presence or severity. These nonverbal patients may not manifest any symptoms even with severe hypertension.

Hypertension may be associated with the following cardiorespiratory, neurologic, and renal symptoms and nonspecific signs such as lethargy, poor feeding, apnea, and irritability (table 3) [76]. In some instances, the underlying cause of hypertension is also responsible for the associated clinical manifestations.

●Cardiorespiratory signs may include tachypnea, tachycardia, cyanosis, cardiomegaly, mottling, and, in severe cases, heart failure or cardiogenic shock [77,78]. Most resolve with correction of hypertension.

●Neurologic symptoms may include irritability, lethargy, hypotonia, hypertonia, seizures, hemiparesis, nerve palsies, and hypertensive retinopathy (eg, vascular tortuosity, hemorrhages, exudates, and increased ratio of venous to arterial caliber) [79]. Some of these findings may be due to coexisting central nervous system abnormalities, such as intraventricular hemorrhage or cerebral thrombosis. Severe cases may present with hypertensive encephalopathy with initial abnormal state of consciousness (eg, hyperalert, irritable, lethargic, or obtunded). (See "Etiology and pathogenesis of neonatal encephalopathy" and "Clinical features, diagnosis, and treatment of neonatal encephalopathy".) [78]

●Kidney abnormalities may include oliguria, polyuria, hematuria, sodium wasting, renal or bladder enlargement, and nephrotic-range proteinuria [80]. Acute kidney injury (AKI) is associated hypertension [14].

DIAGNOSIS — Persistent systolic and/or diastolic blood pressure (BP) values that exceed the 95^th percentile for postmenstrual age (figure 1 and table 1) should be considered abnormal and should be investigated. The first step in the evaluation is to confirm the diagnosis of hypertension by repeated, accurate measurements. In general, a diagnosis of hypertension is supported by three or more elevated BP measurements over a 6- to 12-hour period. As noted previously, a standardized protocol for BP measurement when oscillometric devices are being used will help to ensure that accurate readings are obtained [5]. (See 'Our approach' above.)

EVALUATION — Once the infant is considered to be hypertensive, an evaluation is performed to identify the underlying cause of hypertension, which may potentially be corrected. This includes a focused history, followed by physical examination and selected laboratory testing and imaging studies.

History — A focused history reviews pertinent prenatal exposures, neonatal course, and concurrent conditions. (See 'Etiology' above.)

●Prenatal history examines the possibility of maternal use of prescribed and illicit drugs, history of perinatal asphyxia, or prenatal ultrasound findings indicative of congenital kidney or urologic disease.

●Neonatal history reviews the use of an umbilical arterial catheter (UAC), current and past medications, and presence of concurrent conditions associated with hypertension (eg, bronchopulmonary dysplasia, and congenital anomalies and/or syndromes associated with hypertension).

Physical examination — The physical examination may indicate the primary etiology of hypertension and may also detect pathophysiologic effects of hypertension, such as heart failure, hypertensive retinopathy, or a neurologic abnormality.

●Four-extremity blood pressure (BP) measurements – All infants with hypertension should have BPs measured in all four extremities to rule out coarctation of the aorta or an aortic thrombus occluding the thoracic or abdominal aorta. In these conditions, the femoral pulses typically are decreased or absent. (See "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Blood pressure and pulses'.)

●Abdominal examination – Abdominal distension or mass might be indicative of obstructive uropathy, polycystic kidney disease (PKD), or abdominal/kidney tumors.

●Extremities – Signs of peripheral thrombi (eg, "cath toes," bluish discoloration of the toes caused by decreased perfusion) may sometimes be seen in hypertension associated with a UAC.

●Genitalia – Newborns with CYP11B1 deficiency typically have ambiguous genitalia in females (clitoral enlargement, labial fusion, formation of a urogenital sinus) and penile enlargement in males. (See "Uncommon congenital adrenal hyperplasias", section on '11-beta-hydroxylase deficiency' and "Causes of differences of sex development", section on 'Adrenal overproduction of androgens'.)

●Dysmorphic feature – Dysmorphic features may suggest an underlying syndrome (eg, Williams syndrome) that includes hypertension as one of its clinical manifestations. (See "Williams syndrome".)

●Neurologic examination – Neurologic examination looking for signs of central nervous system dysfunction (eg, irritability, lethargy, or obtundation) that is consistent with hypertensive encephalopathy and warrants immediate treatment [78]. (See "Management of hypertension in neonates and infants", section on 'Severe symptomatic hypertension'.)

●Cardiovascular findings – Tachycardia, tachypnea, and poor perfusion manifested by cool and mottled extremities, decreased capillary refill, decreased peripheral pulses, and lowered systemic BP may be indications of heart failure and warrant ongoing immediate evaluation (eg, chest radiograph, echocardiograph) and treatment [78]. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation' and "Heart failure in children: Management".)

Newborns with hyperthyroidism may have tachycardia, flushing, and low birth weight. (See "Evaluation and management of neonatal Graves disease", section on 'Clinical manifestations'.)

Laboratory testing — Often, the underlying cause is identified by the history and physical examination. Initial laboratory testing is directed toward whether kidney disease is present. Routine testing includes urinalysis; urine culture; and measurement of blood urea nitrogen and serum creatinine, electrolytes, and calcium.

In some infants with renal artery thrombosis or embolism associated with a UAC, hypertension may occur in the absence of hematuria, proteinuria, or azotemia. Thus, their absence does not exclude this etiology. Conversely, mild and transient hematuria and proteinuria are common and nonspecific findings in ill newborns and they cannot be used to diagnose renovascular disease.

Further testing is guided by the initial evaluation and individualized for the infant and may include measurement of thyroid function tests, serum aldosterone, and plasma renin activity. Other studies may be needed to detect neurologic, drug, endocrine, or metabolic causes of neonatal hypertension.

Imaging studies

●Ultrasound – Kidney ultrasonography with Doppler evaluation is the imaging modality of choice in neonatal hypertension and should always be obtained as part of the initial evaluation, when the cause has not been ascertained by the initial evaluation. It can identify kidney masses, urinary tract obstruction, tumors, calculi, and cystic kidney disease. Doppler flow studies can assist in detecting renal and aortic thrombi and in monitoring their course. Doppler studies are also essential to the diagnosis of renal venous thrombosis.

●Renal scans – Radionuclide imaging is sometimes recommended when sonography is nondiagnostic. While a variety of isotopes are available to evaluate differential renal blood flow and glomerular filtration, useful diagnostic images are difficult to obtain in the neonatal period due to the immaturity of kidney function. Given this, it may be best to defer radionuclide imaging until the infant has reached at least 44 weeks postconceptional age, or even later. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Dynamic renal scan' and "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Static renal scan'.)

●Angiography – In infants with severe hypertension and no etiology detected by sonography, angiography should be considered. Although this test is invasive, it is the gold standard for the diagnosis of renovascular hypertension. Institutional expertise should guide the decision to perform angiography. In many instances, it will be appropriate to control the hypertension medically until the baby reaches a size at which angiography can be performed safely [81]. Noninvasive renal angiography, including computed tomography and magnetic resonance imaging, should not be routinely ordered in infants, because these techniques do not have sufficient resolution to reveal branch vessel disease in this age group.

Echocardiography — An echocardiogram should be obtained to detect possible left ventricular hypertrophy, left ventricular systolic dysfunction, or left atrial dilation and aortomegaly [7,23]. As in older children, detecting cardiac involvement would favor early institution of treatment with antihypertensive medications [21]. (See "Management of hypertension in neonates and infants", section on 'Who should be treated?'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in children".)

SUMMARY AND RECOMMENDATIONS

●Definition – The diagnosis of hypertension should be considered in a neonate with persistent systolic and/or diastolic blood pressure (BP) values that exceed the 95^th percentile for postmenstrual age (figure 1 and table 1). (See 'Definition' above.)

●Incidence – The incidence of neonatal hypertension varies depending on the clinical setting. It is uncommon in healthy term infants, with a reported incidence of 0.2 percent. The incidence is higher in infants who are admitted to the neonatal intensive care unit (NICU; 0.7 to 3 percent), especially in very preterm ill infants who are more likely to have risk factors for hypertension (eg, umbilical arterial catheter [UAC] placement and bronchopulmonary dysplasia). (See 'Incidence and risk factors' above.)

●Measurement – BP can be measured either directly through intraarterial measurement or noninvasively (eg, oscillometry). Each center that cares for neonates should establish a standard approach for obtaining BP to ensure accuracy and consistency. In our center, we obtain BP measurements while the infant is either asleep or in a quiet state and in a prone or supine lying position. For noncritically ill infants, BP is measured by an oscillometric device after an appropriately sized BP cuff is positioned on the right upper arm and preferably 1.5 hours after a feed or medical intervention. (See 'Measurement' above.)

●Etiology – There are numerous causes of neonatal hypertension (table 2). The most common etiology is UAC-associated thromboembolism, followed by chronic lung disease and kidney disease. (See 'Etiology' above.)

●Clinical features – Most hypertensive newborns are asymptomatic. In those who are symptomatic, the magnitude of hypertension may not correlate with its presence or severity. Hypertension may be manifested by cardiorespiratory, neurologic, and renal symptoms and nonspecific signs such as lethargy, poor feeding, apnea, and irritability (table 3). (See 'Clinical features' above.)

●Diagnosis – The diagnosis of hypertension is confirmed by repeated accurate measurements that demonstrate either systolic or diastolic BP that persistently exceeds the 95^th percentile for postmenstrual age (gestational age at birth plus chronologic age) (figure 1 and table 1). (See 'Diagnosis' above.)

●Evaluation – Once the diagnosis of neonatal hypertension is confirmed, an evaluation is performed to identify the underlying cause of hypertension, which may potentially be corrected. This assessment includes a focused history, followed by physical examination and selected laboratory testing and imaging studies. (See 'Evaluation' above and "Management of hypertension in neonates and infants", section on 'Correcting underlying cause'.)