ARTICLE

Common Clinical Scenarios of Systemic

Hypertension in the NICU
Sheema Gaffar, MD, MS,*† Rangasamy Ramanathan, MD,* Molly Crimmins Easterlin, MD, MS†
*Division of Neonatology, Department of Pediatrics, Los Angeles General Medical Center, Keck School of Medicine, University of Southern California, Los
Angeles, CA
†
Division of Neonatology, Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los
Angeles, CA

PRACTICE GAPS

The diagnostic criteria and treatment of neonatal hypertension are

inconsistent. Due to an insufficient number of published studies and a lack
of evidence on the long-term effects of hypertension and on the safety and
efficacy of antihypertensive medications, guidelines for the treatment of
hypertension in neonates and infants are lacking. Long-term effects of
neonatal hypertension are also underrecognized, resulting in variable
practices for monitoring and follow-up.

OBJECTIVES After completing this article, readers should be able to:

1. Identify hypertension in a neonate of any gestational age, initiate diagnostic

evaluation, and establish follow-up and long-term monitoring plan.
2. Recognize common clinical scenarios in which neonatal hypertension
can present in the NICU.
3. Describe antihypertensive therapeutic options in neonates.

ABSTRACT
AUTHOR DISCLOSURES Drs Easterlin,
Ramanathan, and Gaffar have disclosed Hypertension affects 1% to 3% of newborns in the NICU. However, the
no financial relationships relevant to this identification and management of hypertension can be challenging
article. This commentary does not because of the lack of data-driven diagnostic criteria and management
contain a discussion of an unapproved/
investigative use of a commercial
guidelines. In this review, we summarize the most recent approaches to
product/device. diagnosis, evaluation, and treatment of hypertension in neonates and
infants. We also identify common clinical conditions in neonates in whom
ABBREVIATIONS hypertension occurs, such as renal vascular and parenchymal disease,
bronchopulmonary dysplasia, and cardiac conditions, and address specific
ACE angiotensin-converting enzyme
AKI acute kidney injury considerations for the evaluation and treatment of hypertension in those
BPD bronchopulmonary dysplasia conditions. Finally, we discuss the importance of ongoing monitoring and
CoA coarctation of the aorta
long-term follow-up of infants diagnosed with hypertension.
ECMO extracorporeal membrane
oxygenation
IV intravenous
PDA patent ductus arteriosus INTRODUCTION
PMA postmenstrual age
SGA small for gestational age
Hypertension is relatively common in neonates in the NICU. Optimal management of
UAC umbilical arterial catheter neonatal hypertension is guided by the etiology of hypertension, determining when

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 pharmacologic intervention is needed, which antihypertensive
medication to use, and treating the underlying cause. However,
identification and management of neonates with hypertension
can be challenging because of a lack of data-driven diagnostic
criteria, limited studies on the long-term effects of hyperten-
sion, and insufficient randomized controlled trials evaluating
the safety and efficacy of antihypertensive medications.
In this review, we summarize the most recent approaches
to the diagnosis, evaluation, and treatment of hypertension
in neonates and infants. We also identify common clinical
conditions in the NICU in which hypertension occurs, in-
cluding renal vascular and parenchymal disease, bronchopul-
monary dysplasia (BPD), coarctation of the aorta (CoA),
postoperative pain and fluid shifts, and prematurity or growth
restriction. We discuss specific management approaches for
each cause of hypertension. Finally, we review the importance
of ongoing monitoring and long-term follow-up of infants di-
agnosed with hypertension.
DEFINITION OF NEONATAL HYPERTENSION
In neonates, blood pressure is variable in the first few days
after birth because of transitional physiology. Generally, in
term infants, blood pressure rises by 1 to 2 mm Hg per day
for the first 3 to 4 days after birth and then levels off. (1) In
preterm infants, blood pressure is more labile and rises rap-
idly in the first few weeks of age, depending on the infant’s
postmenstrual age (PMA), birthweight, and antenatal expo-
sure to medical conditions of pregnancy. (2)(3) In extremely
preterm infants, blood pressure may initially decrease for
the first few hours after birth before increasing (Table 1).
(4)(5)
Due to this expected variability in blood pressure, it
can be difficult to strictly define normal blood pressure
and high blood pressure in the first weeks after birth. In
practice, for a preterm infant, the lowest acceptable mean
arterial blood pressure in the first few days after birth is
approximately equivalent to the gestational age in weeks,
as long as there is clinical evidence of good systemic per-
fusion. (6)(7)(8) Once a neonate is 2 weeks old, the defini-
tion of normal blood pressure is more standardized because
some normative data exist. (9) The American Academy of
Pediatrics recommends using these blood pressure percen-
tiles to define normal blood pressure ranges for infants who
are older than 2 weeks’ chronologic age and 26 to 44 weeks’
PMA (Table 2). (2)(9)(10)(11) Hypertension is typically defined

Table 1. BP Values Obtained on the Newborn Day, 3 Days after Birth, and 5 Days after Birth
Newborn Day BP Day 3 BP Day 5 BP
Birthweight
(g) Average 10th Pc 50th Pc 90th Pc Average 10th Pc 50th Pc 90th Pc Average 10th Pc 50th Pc 90th Pc
#1,000 SBP 56 40 55 72 60 46 59 77 62 49 62 77
DBP 35 21 36 48 40 27 38 56 39 29 38 51
MBP 43 27 41 56 48 35 46 64 47 36 47 59
1,001–1,500 SBP 56 43 55 71 65 53 65 78 67 54 68 79
DBP 35 24 36 45 42 32 42 53 43 33 43 54
MBP 43 31 43 56 51 40 51 61 52 41 52 62
1,501–2,000 SBP 59 48 58 70 65 54 65 77 68 57 68 81
DBP 35 26 35 44 42 33 41 52 42 32 42 53
MBP 44 34 44 54 51 42 51 60 52 42 52 64
2,001–2,500 SBP 60 50 59 72 68 58 68 79 73 60 73 86
DBP 37 27 36 46 44 35 44 53 45 35 44 57
MBP 46 36 45 55 53 44 53 62 56 45 55 69
2,501–3,000 SBP 67 54 64 82 71 59 71 84 73 63 74 83
DBP 43 30 41 58 45 34 44 56 43 35 42 54
MBP 52 40 50 68 55 44 54 67 55 45 54 66
3,001–3,500 SBP 69 56 69 82 74 62 73 87 75 63 75 88
DBP 42 32 42 52 47 37 46 58 46 37 45 56
MBP 52 42 52 63 58 46 57 70 57 48 57 68
3,501–4,000 SBP 70 59 70 81 75 62 74 86 80 69 80 91
DBP 42 32 41 52 48 37 47 59 48 39 48 59
MBP 53 43 52 64 58 46 58 70 60 50 60 71
4,001–4,500 SBP 71 58 70 88 75 62 75 88 77 61 78 90
DBP 43 35 42 54 47 36 45 59 46 36 44 58
MBP 53 43 52 66 58 45 58 71 58 45 58 69
Values are based on birthweight for preterm and term infants, based on a retrospective review of 629 infants in Hungarian NICUs. (4) Before
this study, the 1995 study by Zubrow et al (5) on 608 infants in Philadelphia NICUs was used for blood pressure norms in the first few days
after birth. BP5blood pressure, DBP5diastolic blood pressure, MBP5mean blood pressure, Pc5percentile, SBP5systolic blood pressure.
Reprinted with permission from Kiss et al. (4).

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 Table 2. Blood Pressure Normative Values Obtained for Infants Older than 2 Weeks
Postconceptional Age 50th Percentile 95th Percentile 99th Percentile
44 wk
SBP 88 105 110
DBP 50 68 73
MAP 63 80 85
42 wk
SBP 85 98 102
DBP 50 65 70
MAP 62 76 81
40 wk
SBP 80 95 100
DBP 50 65 70
MAP 60 75 80
38 wk
SBP 77 92 97
DBP 50 65 70
MAP 59 74 79
36 wk
SBP 72 87 92
DBP 50 65 70
MAP 57 72 71
34 wk
SBP 70 85 90
DBP 40 55 60
MAP 50 65 70
32 wk
SBP 68 83 88
DBP 40 55 60
MAP 48 62 69
30 wks
SBP 65 80 85
DBP 40 55 60
MAP 48 65 68
28 wks
SBP 60 75 80
DBP 38 50 54
MAP 45 58 63
26 wks
SBP 55 72 77
DBP 30 50 56
MAP 38 57 63

Infants are at 26 to 44 weeks’ PMA. These values, first published in 2012 by Dionne et al, (9) remain in use presently. DBP5diastolic blood
pressure, MAP5mean arterial pressure, SBP5systolic blood pressure.
Reprinted with permission from Kiss et al. (4).

as persistently elevated systolic, diastolic, or mean blood pres-
sure, greater than the 95th percentile, or any elevated
blood pressure associated with signs or symptoms of or-
gan damage. (6)(10) In the ambulatory setting, persistent
hypertension is defined as hypertension present in more
than 3 office visits. (10) In the intensive care unit, how-
ever, persistent hypertension is vague and often deferred to
the clinician’s judgment.
The technique used in measuring blood pressure is im-
portant as most oscillometric devices are not manufac-
tured specifically for the neonatal population. (12) The
American Academy of Pediatrics, American Heart Associ-
ation, and National Institutes of Health have published
best practice recommendations for blood pressure mea-
surement in infants with an oscillometric device or with
auscultation (manual). (10)(12) Cuff size is selected in re-
lation to the size of the extremity used for measurement;
the right upper arm is typically used for brachial artery
blood pressure measurement, as the left upper arm can
be erroneous in cases of CoA. (10) Although the thigh
can be used for popliteal artery blood pressure measurement
in neonates, the values are not easily compared with pub-
lished reference tables, which use the arm. (10) The length
and width of the cuff should be 80% to 100% and 45% to
70% of the arm circumference, respectively. (10) Measure-
ments should be taken while the infant is calm, laying in the

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 supine position, 1.5 hours after the last feeding, and after the
cuff has been in place for 15 minutes. A repeat blood pres-
sure assessment can be done if the first one is elevated, and
the values can be averaged. (1)(2)(6)(10)(13) An umbilical ar-
terial catheter (UAC) provides direct, continuous intra-arterial
blood pressure measurements that are more accurate than
cuff measurements but also more invasive.
EPIDEMIOLOGY
While the incidence of hypertension varies slightly based
on the definition of hypertension used, it occurs in 1%
to 3% of infants hospitalized in the NICU. (2)(6) It is
more common in the NICU population than in healthy
term newborns where the incidence is 0.2%. (9)(14) Ap-
proximately half (52.8%–57.7%) of neonates diagnosed
with hypertension in the NICU receive pharmacologic treat-
ment with at least 1 antihypertensive medication. (13)(15)
Risk factors for neonatal hypertension include antenatal
factors such as exposure to hypertension of pregnancy, ex-
posure to substance use disorder during pregnancy such as
methamphetamine, and perinatal factors such as exposure
to corticosteroids, as well as preterm birth, low birthweight,
and intrauterine growth restriction. (6) Postnatally, neonates
with increased severity of illness may undergo procedures
such as UAC insertions and extracorporeal membrane oxy-
genation (ECMO), which further increase the risk for hyper-
tension. (10)(11) Additional infant risk factors for hypertension
include renal artery stenosis, renal parenchymal disease, BPD,
CoA, endocrine abnormalities, prematurity, and growth re-
striction. (1)(2)(14)
ETIOLOGY
The most common cause of neonatal hypertension is renal
vascular disease or UAC-associated thrombosis (12)(14)(16)
followed by congenital or acquired renal parenchymal con-
ditions. (1)(10)(12)(15)(17)(18) BPD is the most common
nonrenal cause of hypertension in infants. The most com-
mon cardiac cause of hypertension in neonates is CoA.
Postoperative hypertension can occur in infants with in-
creased thoracoabdominal pressure after abdominal wall
closure or ECMO. Broad neonatal conditions associated with
hypertension include neurologic causes, such as seizures
or intracranial masses, and endocrine diagnoses, such
as hyperthyroidism, mineralocorticoid excess, congenital
adrenal hyperplasia, or genetic etiologies. (12) Despite this
vast number of etiologies, half of neonatal hypertension is
idiopathic. (19)
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PATHOGENESIS
The pathogenesis of hypertension is unique to each clini-
cal condition.
UAC-associated Renovascular Hypertension
UAC-associated thrombosis can result in a partially or
completely occlusive aortic thrombus, from which a large
thrombus or smaller thrombi can embolize into the renal
parenchyma, causing hypertension. (12) Disruption of the
vascular endothelium during placement of the catheter it-
self may also lead to the formation of microemboli, which
may deposit in the renal artery, decreasing perfusion to
the kidney, stimulating renin and aldosterone production,
and causing hypertension secondary to increased sodium
reabsorption and water retention. (20) These microemboli
may be too small to detect on ultrasonography. (12)(14)(16)
Other renovascular abnormalities such as renal artery
stenosis, renal vein thrombosis, and fibromuscular dyspla-
sia are rare but possible causes of neonatal hypertension,
especially in the setting of other common risk factors for
thromboembolic disease such as pregnancies complicated
by diabetes mellitus. (12)(14)
Congenital and Acquired Renal Parenchymal Disease
Congenital anomalies of the kidney and urinary tract can
cause neonatal hypertension by obstructing the urinary
tract. Large cystic kidneys can compress the urinary tract
from the outside, causing obstruction at any level, whereas
obstructions at the ureteropelvic junction and the urethra
are more common from valves or malformations within
the urinary tract itself. (14)(20) Polycystic kidney disease,
multicystic dysplastic kidney disease, and congenital renal
hypoplasia/dysplasia likely cause hypertension because of
the associated abnormal renal parenchyma. (12)(20)(21)
Postnatal renal ultrasonography can confirm these struc-
tural abnormalities, though ideally, these conditions are
known or suspected antenatally. (10)
Acute kidney injury (AKI) is a common yet underdiag-
nosed entity in the NICU that results in acquired renal
parenchymal diseases such as acute tubular necrosis, in-
terstitial nephritis, or cortical necrosis, and subsequent
hypertension from excessive renin release. (12)(14)(20)
Bronchopulmonary Dysplasia-related Hypertension
BPD is the most common nonrenal cause of hypertension
in infants. Hypertension in BPD may be from a combination
of underlying disease and its treatments. Neonates with BPD
are more likely to have vasomotor dysfunction and increased
stiffness of the systemic arteries leading to hypertension.
Vol. 25 No. 1 JANUARY 2024 e39
 (14)(20) This systemic hypertension is likely how neonates
with BPD maintain pulmonary blood supply in the setting of
concurrent pulmonary hypertension and chronic hypoxemia.
In addition, a vast majority of infants with BPD-associ-
ated hypertension were found to have low renin levels,
suggesting that volume excess is a possible contributor to
their hypertension and lung disease. (12)(14)(22)(23)
Treatments for BPD, including corticosteroids and neph-
rocalcinosis-inducing diuretics, may further exacerbate
hypertension. (12)(20)
Coarctation of the Aorta
The most common cardiac cause of hypertension in neo-
nates is CoA. (10) Development of CoA antenatally has
been attributed to decreased blood flow through the aortic
valve and aortic arch causing decreased growth (24) and
postnatally has been attributed to overgrowth of ductal tis-
sue into the aorta causing constriction at those sites. (25)
Normally, blood pressure is 10% to 20% higher in the
legs than in the arms. (10) However, in infants with CoA,
increased pressure is required in the aorta proximal to the
area of coarctation to get blood past the narrowed segment
and to perfuse the lower body. (25) This increased after-
load typically manifests as upper extremity hypertension
relative to the lower extremities. Left ventricular hypertro-
phy and the development of collateral vessels are addi-
tional adaptive mechanisms that develop over time in
response to obstruction in CoA physiology. (24)(25)
Postoperative Hypertension (Pain, Withdrawal, Fluid
Shifts, Compression, Indirect Endocrine Effects)
Agitation due to undertreated pain or sedation withdrawal
may cause hypertension. Postprocedural fluid shifts in the
thoracoabdominal cavity during prolonged surgical proce-
dures can also cause hypertension, (26) particularly after
staged repair of giant omphalocele (27) and ECMO. (28)(29)
An additional mechanism of postoperative hypertension
is endocrine. After abdominal wall closure, increased intra-
abdominal pressure causes renal and adrenal compression, re-
sulting in catecholamine release and subsequent hypertension.
(26)(27) Similar postoperative catecholamine release is com-
mon after surgical repair of CoA as well, termed “paradoxical
hypertension.” (26)(30)(31) The endocrine component of post-
ECMO hypertension is more variable, as some fluid overload
appears to be secondary to impaired water and sodium regula-
tion without evidence of abnormal renin levels, (26) whereas
others have increased renin and endothelin levels along with
oliguria. (28)(29)
Endocrine-related Hypertension
Hyperthyroidism and congenital adrenal hyperplasia are
common endocrine etiologies for hypertension, especially
in the context of abnormal physical examination findings
(Table 3) or elevated thyroid hormone or serum androgen
levels. (10)(32)(33) Endogenous cortisol surges or stress-
dose steroids for adrenally insufficient neonates likely con-
tribute to episodic hypertension as well. Similar surges of
catecholamines and other vasoactive hormones can occur

Table 3. Pertinent Physical Examination Findings

System Finding Possible Etiology
Vital signs Tachycardia Hyperthyroidism
Irregular respiratory rate Intracranial hypertension
Height, weight Poor growth with low percentiles Chronic renal failure
HEENT Elfin facies Williams syndrome
Webbed neck Turner syndrome
Moon facies Cushing syndrome
Proptosis, thyromegaly, goiter Hyperthyroidism
Chest Murmur, thrill, apical heave Structural heart disease, left ventricular hypertrophy
Widely spaced nipples Turner syndrome
Abdomen Abdominal mass Wilms tumor, Neuroblastoma
Palpable kidneys Hydronephrosis
Genitourinary Ambiguous or virilized genitalia Congenital adrenal hyperplasia
Neurologic Anterior fontanelle pulsation Severe intracranial hypertension, Vein of Galen
Skin Pallor, flushing, diaphoresis Pheochromocytoma
Cafe-au-lait spots Neurofibromatosis
Adenoma sebaceum Tuberous sclerosis
Malar rash Neonatal lupus erythematosus

These findings suggest an etiology beyond the common hypertensive phenotypes in the NICU. (10) HEENT5head, ears, eyes, nose, and
throat examination.
Adapted from Flynn JT, Kaelber DC, Baker-Smith CM, et al; Subcommittee on Screening and Management of High Blood Pressure in Chil-
dren. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;
140(3):e20171904. (10)

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 as a result of compression from intra-abdominal masses,
tumors (ie, neuroblastoma, Wilms tumor), and operations,
as noted above. (26)
Prematurity or Growth Restriction
Preterm and/or growth-restricted small for gestational age
(SGA) neonates are at an increased risk for hypertension
because of renal immaturity and vascular maldevelopment.
When an infant is born early, in utero renal development is
interrupted, resulting in reduced numbers of nephrons and
glomeruli, making these neonates particularly vulnerable
to postnatal injuries from hypoxia, hypotension, or nephro-
toxins. (14) Preterm birth also interrupts normal vasculo-
genesis, causing decreased elastin production. (16)(34)(35)
Similarly, a fetus with growth restriction secondary to preg-
nancy complications, such as malnutrition or hypertension,
may require increased circulatory pressure to maintain per-
fusion in the setting of high in-utero afterload. (14)(17)
Persistence of this hypertensive state after birth, despite res-
olution of the antenatal environment, highlights the de-
creased arterial compliance that develops with growth
restriction. When these infants undergo subsequent ac-
celerated catch-up growth, increased fluid and sodium
demands worsen their hypertension. (14)(18) Decreased
serum insulinlike growth factor 1 levels in SGA infants
have been shown to affect central aortic elastic proper-
ties and structure, resulting in decreased compliance
and hypertension. (36)
Low-birthweight infants are prone to develop hyperten-
sion after exposure to steroids because of increased gluco-
corticoid sensitivity, a mechanism that may be mediated
by placental 11b-hydroxysteroid dehydrogenase or endothe-
lial nitric oxide synthase. (6)(17) Antenatal glucocorticoid
exposure, particularly within 7 days of birth, results in
decreased glomerular filtration and increased levels of
angiotensin-converting enzyme (ACE) and angiotensin-II,
whereas postnatal exposure manifests as myocardial dys-
function and systemic hypertension from renin-angiotensin-
aldosterone system dysregulation. (17)(35)
There can be a few iatrogenic reasons for neonatal hyper-
tension in the setting of prematurity. Preterm infants often
require parenteral nutrition, placing them at risk of receiving
excessive water, sodium, calcium, and vitamin A/D. (14)(18)
Medications such as caffeine and phenylephrine or atropine
mydriatic ophthalmic drops further increase the risk of hy-
pertension in this cohort. (37) Environmental phthalate
exposure from noninvasive respiratory support equip-
ment, (22)(38) parenteral nutrition storage bags, (18) and
intravenous (IV) line tubing (18)(22) has recently been
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identified as a potential contributor to neonatal hyperten-
sion through increased activation of the mineralocorti-
coid receptors, although more research is needed to further
define this purported effect. (19)(39)(40)
PRESENTATION
Hypertension in neonates is generally asymptomatic and
is usually an incidental observation on routine monitoring.
However, there are specific clinical scenarios that have addi-
tional elements to the presentation of neonatal hypertension.
These common conditions can often be identified by patient
examination and history review.
UAC/Vascular and Renal Parenchymal Factors
Presentation of renal-related hypertension in the NICU
can occur at any time. When occurring in the first 2 weeks
after birth, in situ UAC (20)(41) and severe bilateral con-
genital renal parenchymal diseases such as autosomal re-
cessive polycystic kidney disease (21) are the most likely
suspects. Unilateral renal conditions and thromboembo-
lism may be seen in neonates after this period, because
symptoms take time to manifest. (21) Severe refractory hy-
pertension in a neonate that requires multiple antihyperten-
sive agents suggests congenital conditions such as polycystic
kidney disease or hormone-producing tumors if hyperten-
sion occurs with concurrent hypercalcemia. Physical exami-
nation finding of the abdominal bruit is specific for renal
artery stenosis, whereas the rare but specific triad of gross
hematuria, thrombocytopenia, and palpable flank mass sug-
gests renal vein thrombosis.
BPD-associated Hypertension
BPD-associated hypertension typically presents later dur-
ing the NICU hospitalization, ranging from 40 weeks’
PMA to a median of 4 months’ postnatal age. (14)(23)
While there is a known association between BPD and risk
of hypertension, (42) presentation can be as subtle as a
5 mm Hg increase in blood pressure compared to age-
matched infants, (43) without any correlation between
the severity of BPD and severity of hypertension. In addi-
tion, hypertension resolves independently of the lung dis-
ease, with resolution by 12 months’ postnatal age in most
cases. (14)(23)
Coarctation of the Aorta
Typically, neonatal coarctation presents with upper ex-
tremity blood pressures 10 to 20 mm Hg higher than
lower extremity blood pressures, with larger gradients con-
cerning for longer segments of narrowing. (10)(24) The
Vol. 25 No. 1 JANUARY 2024 e41
 decreased amount of blood perfusing the lower extremities
can also present as a brachial-femoral pulse delay. (25)
However, depending on the location of coarctation,
neonates with CoA can also present with no blood pres-
sure gradient if they have a patent ductus arteriosus
(PDA) and no obstruction at the time of blood pressure
measurement (Table 4). This scenario results in normal
pulse oximetry values and a passed critical congenital heart
disease screen in the nursery or during short NICU stays.
(10)(24)(25) In these patients, symptoms may develop after
hospital discharge or may remain undetected at home as
the ductus arteriosus constricts and closes, creating critical
CoA. (44) Because the left ventricle does not have time to
adapt to the increased afterload by hypertrophying and gen-
erating collateral circulation, these neonates may present in
shock, with florid signs of heart failure including hepato-
megaly, oliguria, lethargy, pulmonary edema, hypotension,
and cardiovascular collapse. (14)(25) If a CoA has been sur-
gically repaired and the infant develops new or worsening
upper extremity hypertension, re-coarctation should be sus-
pected. (10)(44)
DIAGNOSTIC EVALUATION
Once hypertension has been identified, diagnostic evalua-
tion includes the following (10)(12)(20)(22)(25)(37):
• Pertinent antepartum history and neonatal history, in-
cluding a history of postnatal invasive procedures
• Four-extremity blood pressure, with the infant in a calm
state
• Complete physical examination with attention to find-
ings that suggest an uncommon etiology (Table 3) or
end-organ damage to the kidneys, heart, eyes, and
central nervous system (ie, brachial-femoral pulse de-
lay, AKI, left ventricular hypertrophy, hypertensive ret-
inopathy, encephalopathy, altered mental status, or
seizures)
• Evaluation of medications (corticosteroids, anticholinergic
eye drops, vasoactive infusions, parenteral nutrition con-
tents, opioid wean) and relative infant state (comfortable,
Table 4. Instances When CoA Does Not Present with Blood Pressure Differential. (10)(24)(25)
Four-Extremity Blood Pressures
No gradient
No gradient between the right arm and the right leg (10) or
higher blood pressure in the left arm than the right arm (25)
No gradient between the right arm and the right leg (10)
No gradient between the left arm and the left leg (10)
CoA5coarctation of the aorta, PDA5patent ductus arteriosus.
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calm, sleeping versus agitated because of pain or hunger
versus discomfort because of opioid withdrawal symptoms,
edema, work of breathing)
• Laboratory studies:
8 Serum laboratories: Electrolyte panel, including
calcium, urea, and creatinine to evaluate for kid-
ney disease
8 Urine studies: Urinalysis for hematuria or proteinuria;
urine calcium and creatinine measurement; and urine
culture if there are anatomic risk factors or a history
of urinary tract infection
• Imaging:
8 Echocardiography to evaluate for structural heart dis-
ease, CoA, left ventricular hypertrophy, left ventricle
systolic dysfunction, and left atrium dilation
8 Renal ultrasonography to evaluate for parenchymal or
structural abnormalities with Doppler of renal arteries
and renal veins; ultrasonography of abdominal aorta if
there is a history of UAC
Consultations to consider are as follows:
• Pediatric nephrology
• Pediatric cardiology for the evaluation of cardiac struc-
ture and function
• Pediatric interventionalist or pediatric cardiac surgeon if
concern for CoA or renovascular thromboembolism, al-
though the degree of intervention may be limited by
size
• Pediatric ophthalmology if concerns for hypertensive ret-
inopathy
Other studies to consider are as follows:
• Cranial ultrasonography to evaluate for intracranial hem-
orrhage, mass, and cerebral edema
• Thyroid function tests
• Cortisol level
• Renin and aldosterone levels
• Adrenal steroid hormone levels to determine specific en-
zyme deficiency (particularly 17-hydroxyprogesterone if
there is high suspicion for congenital adrenal hyperpla-
sia secondary to 21-hydroxylase deficiency)
Likely Anatomy
Left or right aortic arch with PDA and CoA (10)(24)
Left aortic arch and aberrant origin of the right subclavian artery
distal to the CoA (10)(25)
Right aortic arch with stenosis in the transverse arch proximal to
the right subclavian artery (10)
Left subclavian artery is hypoplastic or stenotic or arises distal to
the CoA (10)(25)
 • Karyotype to determine genetic sex
• Results of the newborn metabolic screen, specifically for
thyroid level, as well as acylcarnitine, free carnitine, and
ornithine, which are metabolites that are associated with
maternal diabetes mellitus and hypertensive disorders that
affect the neonate (45)
• Urinary catecholamines if suspicion for pheochromocy-
toma or neuroblastoma
• Urinary phthalate levels
GENERAL MANAGEMENT APPROACH
Due to small-scale studies and a lack of evidence on the
long-term effects of hypertension and on the safety and ef-
ficacy of antihypertensive medications, guidelines for the
treatment of hypertension in neonates and infants are
lacking. (36) As such, the treatment of neonatal hypertension
relies on expert consensus and research pertaining to the
treatment of childhood, adolescent, and adult hypertension,
which does not always translate well to neonates. (12)
Nonpharmacologic treatment begins by assessing modifi-
able factors such as fluids, medications, and pain. Volume-
overload states may be treated by decreasing IV fluids, and
high-afterload states may be treated by decreasing the doses of
inotropes, vasopressors, and calcium infusions. Other states of
discomfort that contribute to elevated blood pressure such as
opioid withdrawal or inadequately controlled pain can be
treated with analgesic medications. (1)(2)(16)
Given the lack of clear guidelines regarding pharmaco-
logic treatment, experts suggest the definitions and treat-
ment thresholds shown in Table 5. (9)(12) Generally, the
decision to initiate antihypertensive treatment focuses on
the following 3 factors: blood pressure percentile for PMA,
clinical status, and evidence of end-organ damage. (2)(12)
Experts recommend that an asymptomatic neonate with a
systolic pressure consistently between the 95th and 99th
percentiles (Table 1 if <2 weeks old; Table 2 if >2 weeks
old) and with no end-organ involvement may be observed
and does not require treatment because of expected resolution
over time in most cases. (1)(12)(46) However, if blood pres-
sure continues to remain above the 99th percentile despite
addressing correctable causes (2)(6)(12)(14) or if there is evi-
dence of end-organ damage at any blood pressure percentile,
experts advocate antihypertensive treatment to prevent adverse
effects. (1)(9)
The optimal time course over which blood pressure
should be reduced is also not well-established for neonates
because of limited data on the treatment of severe hyper-
tension in neonates. Extrapolating from pediatric guide-
lines intended for the ambulatory setting suggests blood
pressure should be treated until it is below the 90th per-
centile to minimize end-organ damage. (12) However, the
approach from a recent pediatric case series (January 2023)
(46) may be more applicable to infants in intensive care
units, although it has not been studied in neonates. This
case series on previously normotensive patients (age 1
month to 18 years) with hypertensive emergency admitted
to the pediatric intensive care unit suggested a controlled
reduction of blood pressure to the 95th percentile over the
course of 2 days to account for a delayed return of cerebral
autoregulation. (46) The rationale behind this approach is
applicable to preterm neonates who are at risk of intracra-
nial hemorrhage because of fragile periventricular vessels
and was successfully executed in 28 preterm and term infants,
as described in the case series. (12)(37)(46)(47) Additional

Table 5. Clinical Definitions and Treatment Thresholds

BP Percentile for End-Organ
Stage PMA Clinical Status Involvementa Treatment Type of Treatment
Normal <95th percentile – – No –
Mild hypertension 95th–99th percentile Healthy No No, observe –
Hospitalized or CKD No Consider treatment Oral or IV
Moderate 95th–99th percentile Healthy Yes Treat Oral
hypertension Hospitalized or CKD Yes Treat Oral or IV
Severe >99th percentile Healthy No Treat Oral
hypertension Healthy, hospitalized, Yes Treat IV
or CKD
Hypertensive SBP >120 or DBP Healthy, hospitalized, – Treat IV infusion
emergency >90 (term) or or CKD
hypertension DBP >80
(preterm)

The definitions and treatment thresholds were proposed in 2019 by Harer and Kent (12) based on data from the Dionne et al (9) study on
infants older than 2 weeks.
BP5blood pressure, CKD5chronic kidney disease, DBP5diastolic blood pressure, IV5intravenous, PMA5postmenstrual age, SBP5systolic
blood pressure.
a
End-organ involvement: left ventricular hypertrophy, altered mental status, and acute kidney injury.
Reprinted with permission from Kiss et al. (4).

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 considerations for neonates include the relative immaturity of
neonatal kidneys and AKI, warranting more caution when us-
ing antihypertensives that are cleared by the kidneys. (14)(16)
Consultation with a pediatric nephrologist with experience in
this population may be helpful in this situation. (12)
ANTIHYPERTENSIVE AGENTS
Common pharmacotherapeutic interventions include thia-
zide and loop diuretics, ACE inhibitors, calcium channel
blockers, b-blockers, and vasodilators. (37) Generally, IV
agents should be used if there are signs of end-organ dam-
age, and continuous infusions are recommended for the
ability to quickly titrate dosing and closely control blood
pressure swings. (28) When initiating and titrating IV an-
tihypertensive therapy, care should be taken to reduce
blood pressure slowly to avoid cerebral ischemia and hem-
orrhage. (48) If the infant is able to tolerate enteral medi-
cations in the absence of severe hypertension, oral/enteral
antihypertensive agents can be considered. Agents with a
long half-life and slower onset of action are most appropri-
ate for hemodynamically stable neonates. (12)(16)
Diuretics
• Diuretic therapy helps treat hypertension and improves
pulmonary function in infants with BPD. (14)
• Thiazide diuretics (such as chlorothiazide and hydrochloro-
thiazide) are commonly used in the NICU because of ease
of administration and less frequent electrolyte disturbances
(37) as compared to loop diuretics (ie, furosemide) that can
lead to an increased risk of electrolyte derangements (ie,
hyponatremia, hypochloremia, metabolic alkalosis, hypocal-
cemia, hypomagnesemia) and nephrocalcinosis because of
hypercalciuria. (12)
• The aldosterone receptor antagonist spironolactone may
have an adjunct role in the treatment of BPD-associated
hypertension because of its potassium-sparing mecha-
nism; however, it has a weak diuretic activity. (14)(19)(23)
b-Blockers
• Propranolol is a nonselective b-1 and b-2 blocker that
may be given orally for the treatment of hypertension; a
rare adverse effect of propranolol is bradycardia.
• Labetalol is a combined b and a-1 blocker with a rapid
onset of action. It is given intravenously and can be
used to treat acute hypertension in a patient who cannot
have enteral medications. It is useful because it does not
cause tachycardia. (12)
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• Esmolol is a very short-acting IV cardioselective b-blocker
that is ideal for the treatment of hypertensive infants with
CoA. (26)
• b-blockers should generally be avoided in infants with
BPD because of the risk of bronchoconstriction. (14)
Calcium Channel Blockers
• Amlodipine and isradipine are enteral calcium channel
blockers. Both medications are easy to administer to in-
fants in compounded solution form and do not require
intensive electrolyte monitoring. (14)
• Due to its shorter duration of action, isradipine can be
initiated for BPD-associated hypertension, with a transi-
tion to amlodipine once blood pressure is controlled. (14)
• Nicardipine has a short half-life and causes peripheral
vasodilation. It is given as a continuous IV infusion and
is particularly useful for infants on ECMO with severe
hypertension. (28)
• Of note, in situations with acutely depressed myocardial
contractility, caution is advised with calcium channel
blockers because calcium influx is a key component of
the cellular action potential.
Vasodilators
• Hydralazine is a vasodilator that can be used for inter-
mittent IV treatment of a patient who cannot tolerate en-
teral medications; however, it may lead to an abrupt
decrease in blood pressure. (12)
• Sodium nitroprusside is also an IV infusion that can be use-
ful for infants on ECMO with severe hypertension refractory
to nicardipine, although there is a risk of toxic metabolite
accumulation (cyanide, thiocyanate, and methemoglobin)
(47), especially in cases of decreased kidney or liver func-
tion. (48)
ACE Inhibitors/Angiotensin Receptor Blockers
• This class of antihypertensives is contraindicated in pa-
tients with bilateral renovascular disease or with solitary
kidney and is generally not recommended for infants
less than 44 weeks’ PMA because of potential adverse
effects on renal development. (11)(20)(48)
• ACE inhibitors and angiotensin receptor blockers can
cause hyperkalemia, AKI, and hypotension; these agents
should be used with extreme caution. When using ACE
inhibitors in preterm infants, consultation with pediatric ne-
phrology is recommended for assistance in determining the
starting dose because of known exaggerated/prolonged hy-
potensive response. (12)(26)
 • In specific situations of older infants with systemic hy-
pertension and concurrent impaired left ventricular dia-
stolic function, enalapril may have a role in improving
ventricular dysfunction, as shown in a small observa-
tional case series of 11 infants who had resolution of hy-
pertension to the 95th percentile and improved left
ventricular diastolic dysfunction on serial echocardio-
grams after 2 weeks of enalapril treatment. (35)
• Captopril has been studied in neonates, with a starting
dose one-tenth of the normal pediatric starting dose,
and close monitoring for hyperkalemia and AKI. (48)
PROGNOSIS, FOLLOW-UP, AND LONG-TERM
MONITORING
Although more than 50% of neonates in the NICU with
hypertension require antihypertensive medications, (13)(15)
most neonatal hypertension resolves by 1 to 2 years of age.
(1)(16)(20) Treatment duration most commonly ranges
from 10 days to 8 to 12 months, (12)(14)(15) with almost all
patients normotensive and off pharmacologic therapy by
24 months’ postnatal age. (20)
Long-term outcomes of neonatal hypertension are not
fully known. (12) The American Academy of Pediatrics rec-
ommends routine blood pressure monitoring in all children
after NICU discharge because of increased risk of develop-
ing hypertension, cardiovascular complications, and chronic
kidney disease in childhood and beyond. (2)(10)(34)(35) For
affected neonates without an etiology for neonatal hyperten-
sion, it is unclear how long the hypertension will persist.
(12) What is clear, however, is the need for follow-up and
ongoing blood pressure monitoring of these patients, as 1%
to 5% of all neonates are hypertensive on follow-up after
NICU discharge, with up to 7.3% remaining hypertensive
at 3 years of age. (10)(14)(49)
In addition, neonates with UAC/vascular thrombosis,
renal parenchymal disease, BPD, CoA, and prematurity or
SGA, are at risk for hypertension later in life, even if their
neonatal hypertension resolves. (16) As such, they require
ongoing general pediatric follow-up to monitor for the re-
currence of hypertension. (11) Some may require further
subspecialty care to evaluate for complications of their
neonatal hypertension, such as retinopathy or congestive
heart failure. (37)(50)
UAC/Renovascular and Renal Parenchymal Disease
Hypertension from vascular thrombosis or AKI eventually
resolves once the inciting agent is removed and the throm-
bus has resolved. (1) However, despite the resolution of hy-
pertension in the NICU, preterm infants with AKI are
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more likely to develop hypertension after NICU discharge,
at 22 to 26 months of age, (14)(51) and may be at increased
risk of developing chronic kidney disease. (52) This under-
scores the importance of diagnosing hypertension in the
NICU so that appropriate follow-up screening and care can
be provided.
Nephrology follow-up, in particular, is recommended for
infants with congenital renal parenchymal disease, obvious
renal anomalies, and some forms of renovascular hyperten-
sion such as renal artery stenosis and renal vein thrombosis
because of the likelihood of persistent hypertension requir-
ing potentially prolonged treatment with antihypertensives
or interventions such as stenting. (2)(10)(12)
BPD-related Hypertension
Most BPD-associated hypertension resolves by 2 years of age,
and antihypertensives can be discontinued by 8 to 12 months
of age. (2)(12) A small number may have persistent hyperten-
sion, increasing risk of chronic kidney disease later in life.
(14)(23) In addition, up to half of infants with BPD-associated
hypertension may first present with elevated blood pressure
after NICU discharge, highlighting the importance of on-
going blood pressure monitoring in infants with BPD.
(9)
Coarctation of the Aorta
Infants with hypertension related to congenital heart dis-
ease and abnormal cardiac anatomy are at increased risk
of developing hypertension that persists into childhood,
(2) even after repair of the heart disease. (53) This risk
is even higher in those with a history of preterm birth
and CoA specifically, despite neonatal surgical repair.
(10)(44)(54) The risks of persistent hypertension and re-co-
arctation are why follow-up is recommended by the American
Academy of Pediatrics and the American Heart Association.
(6)(10)(24) If any suspicion for CoA exists in a newborn after
discharge, follow-up with a pediatric provider who will evalu-
ate pulses, measure 4-extremity blood pressures, and have a
low threshold for echocardiographic evaluation is imperative.
(24)(25)
Postoperative Hypertension
Most cases of postoperative hypertension resolve, but in rare
cases, neonates with repaired giant omphaloceles may need
antihypertensive therapy after NICU discharge, requiring
outpatient follow-up with a provider able to manage and
wean those medications. (27)(37)
Vol. 25 No. 1 JANUARY 2024 e45
 Table 6. Management Considerations for Common Clinical Conditions of Hypertension in the NICU.
Recommended
Follow-up for
Surveillance and
Clinical Context Timing of Specific Aspects of Pharmacologic Management Management of
of Hypertension Presentation Presentation Treatment Considerations Hypertension
UAC or First 2 wks after birth: Abdominal bruit, ACE inhibitors If associated with renal Nephrology for
renovascular UAC gross hematuria, contraindicated artery stenosis or renovascular
2 wks after birth: thrombocytopenia, with renovascular aortic thrombosis, abnormalities
thromboembolism flank mass disease the duration of
Heparin or papaverine therapy is weeks to
(reduces the risk of months
UAC thrombosis) Once normotensive for
(20)(34) 4–8 wks and
thrombus is
resolved,
antihypertensive
medication can be
weaned (1)
Renal First 2 wks after May be known ACE inhibitors Postnatal renal Nephrology
parenchymal, birth: severe antenatally contraindicated ultrasonography
congenital, or bilateral Palpable kidneys with solitary kidney (10)
acquired conditions AKI or history of AKI and until at least Avoid nephrotoxins
2 wks after birth: 44 wks’ PMA Some congenital renal
unilateral conditions may
conditions require multiple
antihypertensive
medications (2)(20)
BPD-associated Later during NICU None or a subtle β-blockers Glucocorticoid-induced Pediatrician
hypertension hospitalization, 40 elevation (as little contraindicated hypertension Pulmonology
wks to 4 months’ as 5 mm Hg Diuretics: thiazide (ie, resolves once
PMA above normal), chlorothiazide) treatment is
Mostly resolves by concurrent BPD, or preferred over loop stopped; consider
12 months’ PMA chronic lung diuretic discontinuing
disease Calcium channel or reducing the
blockers dose (1)
Spironolactone Fluid overload and
(emerging role) hypoxemia can
(11)(19)(23) contribute (11)
Aortic coarctation Any time during the Arch obstruction: Prostaglandin infusion Specific situations Pediatrician
newborn period,  Upper extremity (ductal patency) (Table 5) require Cardiology
whether in- hypertension β-blockers close monitoring Cardiothoracic
hospital or at (10–20 mm Hg until PDA is closed surgery
home gradient) (24)
May not be detected  Brachial-femoral Surgery is definitive
by pulse oximetry pulse delay treatment (10)
screening for  Heart failure (ie, Re-coarctation is
critical congenital pulmonary edema, possible, even after
heart disease hepatomegaly, surgical repair
oliguria, lethargy)
and eventual shock
No obstruction:
no gradient in
extremity blood
pressures, may
have murmur of
PDA
Postoperative After procedures for Episodic, may have Adequate sedation Address pain and Pediatrician if
hypertension abdominal wall signs of fluid and analgesia fluid/volume requiring
closure, overload (ie, (11)(29) overload (29) antihypertensive
omphalocele edema), oliguria, Vasodilators: nicardipine Discontinue or reduce medications (27)
repair, or ECMO or agitation/ (preferred) (28) or the dose of
distress nitroprusside (47)(49) inotropes and
for continuous steroids, if possible
infusions; hydralazine
(13) for intermittent
IV doses
Consider labetalol (13)
Continued

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by HINARI BAND 1 user
 Table 6. (Continued)
Recommended
Follow-up for
Surveillance and
Clinical Context Timing of Specific Aspects of Pharmacologic Management Management of
of Hypertension Presentation Presentation Treatment Considerations Hypertension
Endocrine Any time Clitoromegaly in If strong suspicion of Endocrinology Depends on the
female infants, and endocrinopathy, consultation etiology
signs of consider initiating Consider special Endocrinology
hyperthyroidism or treatment while studies (see the
catecholamine results are pending Diagnostic
excess Evaluation section)
Obtain newborn
screen results
Prematurity or Any time May be known ACE inhibitors Evaluate medications Pediatrician
growth antenatally contraindicated and consider Nephrology
restriction Low birthweight until at least discontinuing or
May suggest 44 wks’ PMA reducing doses of
suboptimal in caffeine,
utero environment phenylephrine, or
(ie, obesity, atropine mydriatic
hypertension, ophthalmic drops
malnutrition) (17) (37)
Avoid nephrotoxins
If receiving parenteral
nutrition, evaluate
constituents (free
water, sodium,
calcium, vitamin A,
vitamin D) (11)(18)
If concurrent
myocardial
dysfunction, may
require multiple
antihypertensive
medications (13)

Medication contraindications are in bold. ACE5angiotensin-converting enzyme, AKI5acute kidney injury, BPD5bronchopulmonary dysplasia,
ECMO5extracorporeal membrane oxygenation, PDA5patent ductus arteriosus, PMA5postmenstrual age, UAC5umbilical artery catheter.

CONCLUSION
the normal range of pressures and pressure
Overall, more information is needed on the causes and con- patterns.
sequences of neonatal hypertension to improve recognition • Know the pathophysiology of common scenarios
of the condition. More robust data are needed on long-term
in the NICU in which a neonate presents with
outcomes of neonatal hypertension to provide optimal treat-
systemic hypertension.
ment, monitoring, and follow-up of this chronic condition.
• Formulate a differential diagnosis for neonatal
(1)(12)(37)(55) Based on limited data, we can use blood pres-
hypertension.
sure reference ranges to diagnose hypertension and expert
guidelines to help with treatment decisions for hyperten- • Know the clinical and diagnostic features of an
sion that are common in the NICU (Table 6). Understand- infant with systemic hypertension, including
ing hypertension in the clinical context of the underlying laboratory and imaging studies.
disease or procedures may help management decisions. • Know the management of an infant with systemic
hypertension, including adverse effects.

American Board of Pediatrics

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