Hypertension In Newborn And Children

Dr. S. Ismat Bukhari

HYPERTENSION IN NEONATES

Objectives

1. A standardized protocol for identifying hypertension in the neonate.

2. Characterize the relationship of blood pressure with gestational age, postconceptual age, and birthweight.

3. Characterize the need for blood pressure measurement in neonates who have left neonatal intensive care units.

4. List the causes of most cases of neonatal hypertension.

5. Describe potential complications related to specific antihypertensive agents or too-rapid reduction in blood pressure.

• Defining hypertension or even normotension in the neonate is difficult.

• The initial step is to ensure that the blood pressure (BP) is being measured accurately.

• In both term and preterm infants, normal BP increases with gestational age, postconceptual age, and birth weight.

Incidence

• The incidence of neonatal hypertension is low.

• In the general NICU population, one study found that 0.08% (26/3,179) of infants had hypertension.

• Another study found that hypertension accompanied 2% (20/988) of NICU admissions.

• Some subpopulations, such as those who have bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage, had a greater risk of being diagnosed with this abnormality.

• Although infrequent, hypertension always is abnormal and, thus, merits further attention.

• Hypertension may not be diagnosed in some infants until after discharge from the NICU.

Causes

• Medical disease, anatomic anomalies, and iatrogenic conditions all may contribute to hypertension.

• Most cases of neonatal hypertension are due to renovascular or renal causes.

• In the past, much attention has been placed on umbilical artery catheters as theoretical sources of thromboembolic events that cause areas of infarction and increased renin release.

• Thrombi have been demonstrated to be present on 25% to 81% of catheters studied.

Common causes of hypertension in neonates

• Other renovascular conditions may cause neonatal hypertension.

• The classic presentation of renal vein thrombosis is hypertension, gross hematuria, and an abdominal mass.

• Fibromuscular dysplasia may be present, causing renal artery stenosis.

• When renal artery stenosis is present, there also may be a mid-aortic coarctation and cerebral vascular stenosis.

• Also in the differential diagnosis is mechanical compression of the renal vessels by tumors, hydronephrotic kidneys, or other abdominal masses.

• Renal parenchymal abnormalities also may cause hypertension.

• Autosomal dominant and autosomal recessive polycystic kidney disease (PKD) may present in the neonatal period with enlarged kidneys and hypertension.

• The hypertension may progress even to the degree that the patient may develop congestive heart failure, necessitating bilateral nephrectomies.

• An infant who has unilateral multicystic dysplastic kidney also may present with hypertension, although this is poorly understood because such kidneys are believed to be entirely nonfunctional.

• Unilateral renal hypoplasia also may have this finding, although this is uncommon.

• Additional renal parenchymal diseases that may be found in the evaluation of hypertension are congenital ureteropelvic junction obstruction or ureteralobstruction by other abdominal processes.

• Acquired renal parenchymal disease in the newborn period may cause significant hypertension.

• Acute tubular necrosis, interstitial nephritis, or cortical necrosis all may have this finding, usually because of volume overload or hyperreninemia.

• An especially difficult to manage hypertension can be found in hemolytic-uremic syndrome, which has been described in both term and preterm infants.

• Infants who have bronchopulmonary dysplasia are at particularly increased risk for the development of hypertension.

• Studies have shown that 13% to 43% of affected infants develop systemic hypertension.

• The source of the hypertension is unclear, although chronic hypoxia is believed to play a role.

• Cardiac, endocrine, and neurologic disorders also may contribute to the development of hypertension and should be included in the differential diagnosis.

• The most common cardiac lesion is coarctation of the thoracic aorta.

• Early repair improves the long-term outcome, although hypertension may persist even after the surgical repair.

• Congenital adrenal hyperplasia, hyperaldosteronism, and hyperthyroidism are accompanied by hypertension, and seizures and increased intracranial pressure are common causes of episodic hypertension.

• Of particular importance in any differential diagnosis are iatrogenic causes.

• Prolonged total parenteral nutrition may lead to either salt and water overload or hypercalcemia, both of which can result in hypertension.

• Also included in the iatrogenic category is the undertreatment of pain. Adequate analgesia may be the only antihypertensive needed in these cases.

• Among the maternal causes of neonatal hypertension are cocaine use, which can harm the developing kidneys and lead to hypertension in the neonatal period.

• Hypertension also has been reported with neonatal withdrawal from maternal heroin use.

• Neoplasms are rare in the neonatal period, but they should be considered in the complete differential diagnosis of ypertension.

• Neuroblastoma, Wilms tumor, and mesoblastic nephroma have been reported to cause neonatal hypertension, either from compression of the renal vessels or ureters or through production of vasoactive substances.

Evaluation

• Hypertension may be noted during the routine monitoring of vital signs or it may be found during the evaluation of an ill neonate.

• Life-threatening presentations of hypertension include congestive heart failure and cardiogenic shock.

• Less ill infants may present with feeding difficulties, unexplained tachypnea, lethargy, apnea, irritability, mottling of the skin, or seizures due to hypertension.

• When hypertension is present, obtaining a focused history is the first priority.

• Prenatal exposures such as heroin and cocaine should be noted.

• Concurrent predisposing conditions such as bronchopulmonary dysplasia, central nervous system disorders, patent ductus arteriosus, and hypervolemia(eg, after blood transfusion) should be identified.

• The physical examination should focus specifically on the cardiac and abdominal evaluations.

• A careful set of four extremity BPs may rule out coarctation of the aorta.

• When BP in the lower extremities is lower than in the upper extremities or if the femoral pulses are not palpable, the evaluation should proceed with a cardiac consultation and an echocardiogram.

• Dysmorphic features may indicate the diagnosis of congenital adrenal hyperplasia or Turner syndrome (which is associated with aortic coarctation).

• The presence of a flank mass may indicate ureteropelvic junction obstruction, and an epigastric bruit suggests renal artery stenosis.

• Appropriate initial laboratory studies include urinalysis, complete blood count, electrolytes, blood urea nitrogen, creatinine, and calcium.

• A urine culture is indicated if infection is suspected.

• A plasma renin level also should be obtained, although at present there are few data on what constitutes a normal value in neonates.

• Usually, a significantly elevated renin level indicates the presence of renovascular disease, although this is not always true.

• Common NICU medications, such as aminophylline, may cause a falsely elevated renin level.

• Nephrology consultation may be needed to help interpret the results in perplexing cases.

• Depending on findings of the history and physical examination, additional tests that may be appropriate to obtain are thyroid studies and evaluations of urine vanillylmandelicacid/homovanillic acid, aldosterone, and cortisol.

• A chest radiograph and echocardiogram may be useful if there is concern for congestive heart failure.

• Ultrasonography imaging of the genitourinary tract is a relatively inexpensive, noninvasive, and rapid study that should be performed in all hypertensive infants.

• Surgically correctible cases of hypertension, such as ureteropelvic junction obstruction, will be readily apparent.

• Ultrasonography also is the modality of choice for identifying renal venous thrombosis.

• Additional imaging studies may include abdominal/pelvic ultrasonography, voiding cystourethrography, or aortography.

• Because this final test may be technically difficult in the neonate, it should be obtained only in experienced centers.

• Nuclear scanning has been recommended by some, but it is difficult to obtain accurate, interpretable results in this age group.

Management

• In general, easily correctible causes of hypertension should be addressed initially.

• Pain should be treated, volume overload corrected, and inotropic infusions weaned before considering the administration of any antihypertensive medications.

• Attempts should be made to choose a suitable agent for the specific clinical situation.

• For most acutely ill infants, continuous intravenous infusions are most appropriate.

• Severe hypertension is treated best in this manner because of the wide fluctuations in BP frequently associated with intermittently administered agents.

• Preterm infants who have immature periventricular circulation are at increased risk for cerebral ischemia and hemorrhage from rapidly falling BPs, so care should be taken to correct the hypertension slowly.

• Continuous infusions allow for titration to this desired effect.

• Published experience indicates that nicardipine, labetalol, and nitroprusside are effective continuously infused medicines in this population.

• During infusions, BP should be monitored by an indwelling arterial catheter or by frequently repeated (every 10 to 15 min) cuff measurements, so the dose can be adjusted to prevent profound hypotension or inadequately treated hypertension.

• Mild hypertension may be treated with intermittent intravenous agents in some infants who are not yet ready for oral medicines. Hydralazine and labetalol have been shown to be effective.

• These must be administered carefully, though, because in some infants, even doses at the lower end of the recommended range may cause significant hypotension.

• An especially risky agent in this regard is intravenous enalaprilat, which should be avoided because of its unpredictable antihypertensive efficacy and potential to cause oligoanuria via blockade of the renin-angiotensin axis.

• Oral antihypertensive agents may be considered when the hypertension is less severe or when the infant is ready to be weaned from intravenous therapy.

• Captopril has proven to be effective, although infants should be monitored for profound decreases in their BP when therapy with this agent is initiated.

• When captopril alone is not effective, the addition of a diuretic often yields the desired blood pressure reduction.

• Such an addition is particularly encouraged in infants who have chronic lung disease.

• Beta blockers should be avoided.

• Other recommended oral agents are amlodipine, hydralazine, and isradipine. Isradipine is especially recommended because it takes effect quickly and can be compounded into a stable suspension that can be dosed accurately in even the tiniest infants.

Treatment of hypertension in neonates

• Some hypertension occasionally can be corrected surgically.

• Ureteral obstruction and aortic coarctation are especially amenable to surgical correction.

• Those who have renal artery stenosis may require medical management until they have grown sufficiently to allow for vascular repair.

• As noted previously, nephrectomies may be necessary in some infants who have polycystic kidney disease.

• Surgery after chemotherapy frequently is indicated when a Wilms tumor or neuroblastoma is the cause of hypertension.

• Some recommend the removal of multicystic dysplastic and polycystic kidneys when they are causing hypertension.

Long term outcome and prognosis• The long-term prognosis for infants who have hypertension depends on the

cause of the disorder.

• Often the hypertension resolves over time.

• Some infants may require frequent adjustments of their antihypertensive regimen as their weight increases; others may be weaned from their medicines as they grow out of their dose.

• Home BP monitoring is crucial and should be established for any infant discharged from the NICU on antihypertensive medications.

• Some hypertension persists as the infant grows. Polycystic kidneys and other forms of renal parenchymal disease may continue to cause hypertension. Hypertension due to renal vein thrombosis may persist sufficiently

• to require nephrectomy. The reappearance of hypertension after repair of renal artery stenosis or thoracic coarctation repair should lead to a search for restenosis.

HYPERTENSION IN CHILDREN

Objectives

1. Define hypertension in children, and be familiar with the approach to the diagnosis of hypertension.

2. Recognize important signs and symptoms associated with hypertension and its sequelae, and formulate an appropriate differential when presented with a hypertensive child or adolescent.

3. Initiate an appropriate evaluation, and know when to refer to subspecialty care.

4. Prescribe both non-pharmacologic and pharmacologic antihypertensive therapy to hypertensive children, and be familiar with the various classes of antihypertensive medications available.

• HTN in the pediatric age group is on the rise, now affecting almost 5% of all children.

• One possible explanation for this striking increase in prevalence over the past several decades is the concurrent rise in pediatric obesity, which currently affects 17% of the pediatric population.

Hypertension

• Pediatric HTN is defined as the sustained elevation of either the systolic or diastolic BP at or above the 95th percentile of BP for a child’s age, gender, and height percentile.

• Normal BP: Both systolic and diastolic BPs are less than the 90th percentile or less than 120/80 mmHg, whichever is lower.

• Pre-Hypertension: Systolic or diastolic BP is between the 90th percentile and the 95th percentile, or between 120/ 80 mmHg and the 95th percentile, if 120/80 mmHg happen to be higher than the reported 90th percentile for the individual child based on his or her age, gender, and height percentile.

• Stage I HTN: Systolic or diastolic BP between the 95th percentile and the 99th percentile +/- 5 mmHg.

• Stage II HTN: Systolic or diastolic BP above the 99th percentile +/- 5 mmHg.

• All children age 3 years and older should have their BP measured during each physician visit, whether the visit is for health supervision care, urgent care, or emergency care, at a minimum of once yearly.

• In addition, children younger than age 3 years should also have their BP measured at each visit if they have a comorbid condition that places them at increased risk for HTN

• Particular attention should be given to children who have conditions such as diabetes mellitus, chronic kidney disease, a history of Kawasaki disease (with or without current coronary artery aneurysms), kidney or heart transplantation, chronic inflammatory diseases, human immunodeficiency virus infection, and nephroticsyndrome, because they are at increased cardiovascular risk.

• In addition to regular BP measurement, these children should have additional cardiovascular risk factor assessment conducted at health care encounters.

Pre-hypertensive

• These children should be considered prehypertensive and should be followed closely because of their increased risk of developing sustained HTN.

• They should be counseled on weight management, if indicated, and should be given activity and the Cardiovascular Health Integrated Lifestyle Diet recommendations.

Stage I hypertension

• If the child is asymptomatic, have him or her return for repeat BP measurements on two additional occasions, 1 to 2 weeks apart.

• If stage I HTN is confirmed by averaging all BP measurements obtained, perform evaluation within 1 month.

• If the child is symptomatic, more immediate referral to a pediatric HTN specialist for initiation of evaluation and treatment is indicated.

Stage II hypertension

• If the child is asymptomatic, he or she should undergo evaluation and treatment within 1 week.

• If symptomatic, the child should be referred immediately to the emergency department or an inpatient facility for care.

• Pediatric HTN is largely asymptomatic; however, children may present initially in hypertensive crisis with severely elevated BP and symptoms ranging from nausea and vomiting to ataxia, mental status changes, seizures, and coma, or with symptoms related to the underlying cause of their HTN.

• In addition, some children may experience anxiety during evaluations, which may cause elevate BPs that are in the hypertensive range; yet, when monitored in their home environment, the children have BP measurements in the normal range.

• This phenomenon of “white coat” HTN can be diagnosed with a 24-hour ambulatory BP monitor that obtains many BP measurements taken in a child’s home environment.

• Children who manifest white coat HTN also should be considered at increased risk for the development of sustained HTN and therefore should be followed every 6 months.

Blood pressure measurement

Initial evaluation• All children diagnosed as having HTN should undergo an

evaluation to investigate for secondary causes of HTN.

• Although primary HTN is on the rise, and is the most common cause of HTN among adolescents, secondary HTN is common enough to warrant investigation, particularly in younger children and those with stage II HTN at presentation.

• The initial evaluation should start with a focused history and physical examination. In addition to obtaining a complete review of systems to help narrow the differential diagnosis (Table 3 below), particular attention should be paid to the pastmedical history (including birth history), current medications, family history, and social history.

• current medications, family history, and social history.

• When obtaining the past medical history, it is important to inquire about any previous diagnosis or treatment of HTN. Any recent discontinuation of antihypertensive

• medications, such as b-blockers and a-adrenergic • agonists,[

• can cause severe rebound HTN if discontinued abruptly.

It is important also to determine if the child has any of the following comorbid conditions or syndromes associated with HTN:

Comorbid conditions• Diabetes mellitus• Thyroid disease• Cushing syndrome• Systemic lupus erythematosus• Other rheumatologic disorder

Syndromes • Williams syndrome (associated with

supravalvular aortic• stenosis, midaortic syndrome, renal artery

stenosis,• renal anomalies)• Turner syndrome (associated with

coarctation of the• aorta, renal anomalies, idiopathic HTN)• Tuberous sclerosis (associated with

coarctation of the• aorta, renal artery stenosis, brain tumors)• Neurofibromatosis (associated with

essential and renovascular• HTN)• Polycystic kidney disease, both autosomal

recessive and• autosomal dominant variants

• A previous history of urinary tract infections or unexplained fevers may suggest chronic pyelonephritis and renal cortical scars or reflux nephropathy.

• A recent or relatively remote streptococcal infection of the pharynx or skin, or exposure to enterohemorrhagic Escherichia coli, may indicate a resolving or resolved postinfectious glomerulonephritis or hemolytic uremic syndrome, respectively.

• Henoch- Schönlein purpura can be associated with persistent renal• manifestations, including HTN, even after initial complete resolution of

symptoms. Previous hospitalizations may reveal information on systemic illnesses, exposure to nephrotoxic medications, or evidence of renal injury. Recent injuries should be assessed, because renal or neurologic trauma can lead to HTN as well as associated pain.

• Because prematurity and low birthweight are associated with decreased nephron endowment and HTN, and umbilical catheter placement can lead to renal artery stenosis and renal vein thrombosis, a detailed birth history also should be obtained.

A thorough review of both prescribed and over-thecountermedications may reveal the following possible

causes for elevated BP:

• Corticosteroids• Decongestants/cold preparations• Nonsteroidal anti-inflammatory medications• Herbal medications/supplements• Oral contraceptive pills• Antihypertensive medications (recent discontinuationof these medications)• b-Adrenergic agonists/theophylline• Erythropoietin• Cyclosporine/tacrolimus• Attention deficit disorder medications

• The family history can be helpful in determining the cause of HTN, particularly for children who have monogenic forms of HTN (such as Liddle syndrome, Gordon syndrome, and apparent mineralocorticoidexcess) and renal disease, and can help also with risk stratification.

• As described in the recent Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, This risk is inversely related to the age at the time of event. Children who have this family history should be considered at increased cardiovascular risk.

• Social history should focus on the following: sexual activity (pregnancy, pre-eclampsia); diet (consumption of caffeine, licorice, sodium, nutritional supplements); smoking/drinking/illicit drug history (nicotine, cocaine, amphetamines, anabolic steroids, hencyclidine, methylenedioxymethamphetamine [“ecstasy”]); level of physical activity (obesity); sleep history (snoring, daytime somnolence, difficulty awakening, which may be suggestive of obstructive sleep apnea); and psychosocial history(stress, anxiety).

• After eliciting a detailed history, the evaluation should then progress to a detailed physical examination, paying particularly close attention to findings suggestive of underlying causes

Differential Diagnosis ofHypertension Among Children,by Age

Initial Laboratory and Imaging Evaluation for All Children Who Have Confirmed Hypertension

Additional Tests to Determine Secondary Causes of Hypertension

• If the results of this• initial evaluation are negative in an older child who

has• stage I HTN, particularly if the average BP is close to• the 95th percentile, the child can be given a

diagnosis• of primary HTN. Younger children and those with• more markedly elevated BP (stage II HTN) should

undergo• further testing if the initial evaluation is unrevealing• to exclude secondary causes for HTN

Symptoms Suggesting Underlying Causes of Pediatric Hypertension

Treatment

• Once a child is diagnosed as having HTN and has undergone an evaluation, antihypertensive therapy should be initiated. This therapy should include guidance on lifestyle modification and nonpharmacologic therapy. All children should be counseled on the following heart-healthy lifestyle:

• 1. Weight loss if overweight 2. For children age 5 years or older: participate in at least 1 hour of moderate-to-vigorous exercise jogging, baseball) every day of the week, and vigorous activity (eg, running, singles tennis, soccer) on 3 days per week.

• Decrease sedentary activities such as television watching• and playing video and computer games to less than• 2 hours per day• 4. Institute several dietary changes according to the Cardiovascular• Health Integrated Lifestyle diet and Dietary• Approaches to Stop HTN eating plan (1) such as:• a. Increase intake of fresh vegetables, fruits, and lowfat• dairy foods• b. Reduce carbohydrate, fat, and processed sugar intake• i. For 4- to 18-year-olds: aim for 10% to 30% of total• calories to come from protein, 45% to 65%• from carbohydrate, 25% to 30% from fat• c. Limit or avoid sugar-sweetened beverages• d. Encourage foods with high dietary fiber content• (age þ 5 ¼ number of grams per day)

• Salt restriction

• a. Initially recommend “no added salt,” with the ultimate

• goal of achieving the current recommendation

• of 1.2 g/day total for 4- to 8-year-olds and 1.5 g/

• day total for children age 9 years and older(2)

• 6. Smoking cessation, if applicable

• Children who have not experienced normalization of their BP with the above interventions after 6 months should be started on antihypertensive medications. In addition, children who present initially with secondary HTN, symptomatic HTN, left ventricular hypertrophy, or hypertensive retinopathy, or who have diabetes mellitus, should be started on antihypertensive medications at

• the time of diagnosis, while implementing the same lifestyle interventions. The pharmacologic agent chosen

• should be targeted to the underlying diagnosis, with attention being paid to existing comorbidities.

Medical conditions that warrant specific antihypertensive drug class

• Unless contraindicated, initial therapy with either a calcium channel blocker or an angiotensin-converting enzyme inhibitor could be considered, because these medications are well-tolerated, have a minimal adverse effect profile, and can be dosed once daily. b-Blockers, angiotensin receptor blockers, and diuretics also are acceptable first-line agents for the treatment of HTN in children.

The lowest dose should be started, titrating to effect until the maximum recommended dose is achieved or until the patient experiences adverse effects. At this point, if the BP is not controlled, an additional agent from

Goal of therapy

• The goal of antihypertensive therapy is achievement of normotension, defined as persistent systolic and diastolic BPs below the 95th percentile.

• In children at increased ardiovascular risk (those with chronic kidney disease, diabetes mellitus, post-heart or kidney transplantation, history of Kawasaki disease, chronic inflammatory disease, human immunodeficiency virus infection, or nephrotic yndrome) or end-organ damage (left ventricular hypertrophy or hypertensive retinopathy), the antihypertensive goal is lower.

• These children should be treated to achievesystolic and diastolic BPs below either the 90th percentile or 120/80 mmHg.

Prognosis

• Children who have HTN should be followed closely to evaluate the effectiveness of prescribed antihypertensive therapy, and to reinforce medication adherence and heart-healthy behaviors.

• If available, BP measurements obtained by a school nurse can be useful in titrating medication dosages between clinic appointments and in monitoring therapy.

• Hypertensive children also should be screened intermittently for the development of end-organ damage in the form of left ventricular hypertrophy, hypertensive retinopathy, and microalbuminuria.

• Children who have left ventricular hypertrophy at diagnosis should have a repeat echocardiography completed 6 to 12 months after starting antihypertensive medications to ensure that their left ventricular mass has decreased with therapy.

• Children without evidence of left ventricular hypertrophy at diagnosis also should undergo follow-up echocardiography, because left ventricular hypertrophy can develop relatively quickly, can be seen in children who have presumably good BP control, and cannot be predicted by the severity of a child’s BP elevation.

• Although often clinically silent in childhood, these forms of end organ damage are associated with significant morbidity and mortality in adulthood.

• The presence of any one of these entities signifies increased cardiovascular risk and the need for intensified antihypertensive treatment to reverse these findings and prevent worsening cardiovascular disease.

• Some children will require long-term antihypertensive therapy into adulthood to maintain normotension. However, successful implementation of lifestyle modifications has been shown to be effective in lowering BP in both children and adults, and can allow some children to avoid or discontinue pharmacologic treatment.

• Children who have primary, obesity-related HTN, in particular, may be able avoid or discontinue antihypertensive medications with lifestyle

• modifications. Obese children have been shown to experience significant BP reductions with salt restriction, and weight loss is particularly effective at lowering BP.

• Children who have secondary HTN may experience normalization of BP as their underlying disease process resolves, allowing them to discontinue medical therapy.

• However, when a chronic underlying condition has led to a child’s HTN, complete normalization of BP is less likely and management may require long-term antihypertensive therapy and monitoring.

Thank You