Hypertension: a cause of growth impairment

Abstract

The effects of high blood pressure on growth are not fully understood and while hypertension may be associated with failure to thrive, hypertension causing failure to thrive in children is poorly documented. We describe four children presenting with failure to thrive due to hypertension consequent to various aetiologies. Control of hypertension with appropriate therapy resulted in improved growth. The exact pathogenesis of failure to thrive in hypertensive children is not known. These cases demonstrate the importance of careful measurement of blood pressure in children with failure to thrive.

Introduction

The association of maternal hypertension with intrauterine growth retardation has been well known for a long time.1 However, the relationship between hypertension and poor growth is ill defined. In fact, it is not listed as a cause of failure to thrive in two respected paediatric textbooks.2,3 We describe four children with hypertension who had significant improvement in growth after treatment of hypertension. This finding confirms the importance of careful blood pressure measurement in all children with failure to thrive.

Case 1: (JB)

A 7-year-old boy presented with cough and shortness of breath. Examination revealed a small, thin child (weight 16.1 kg, <0.4 percentile and height 111 cm, 0.4 to 2nd percentile). He was in cardiac failure and all his peripheral pulses were present and equal. His blood pressure was markedly elevated at 210/135 mm Hg. Fundoscopy through dilated pupils was normal apart from a minor degree of swelling affecting the nasal half of the right optic disc. The glomerular filtration rate calculated from height and plasma creatinine (cGFR) was normal as were the serum electrolytes including calcium. Thyroid function, plasma cortisol and urinary catecholamine metabolites were also normal. Supine peripheral plasma renin activity was variably elevated, ranging from 3–29 nmol/l/h (normal range 1–7 nmol/l/h), aldosterone >3300 pmol/l (normal 28–445) and angiotensin II concentration 404 pg/ml (normal 3–12).

Echocardiogram revealed a dilated, poorly contracting and markedly hypertrophied left ventricle with aortic valve thickening and calcification. Renal ultrasound scan showed enlarged kidneys (length on the 95th centile) with markedly echogenic pyramids suggestive of nephrocalcinosis. A renal arteriogram showed a single right and a single left renal artery with no narrowing. There was a peripheral branch stenosis in the upper pole of the right kidney with parenchymal loss in that area. Selective renal vein renin sampling showed a ratio between right and left of 1.57 (normal <1.5).4 He had a normal male karyotype and in situ hybridisation studies were negative for Williams syndrome. A renal biopsy showed 10 of 24 glomeruli to be globally sclerosed and eight to have segmental lesions. Arteries and arterioles showed medial hypertrophy and there was wrinkling of the basement membranes of surviving glomeruli. An attempt at balloon angioplasty failed. The blood pressure was controlled with a combination of atenolol, hydralazine, nifedipine and enalapril. Subsequent echocardiograms showed an improvement in left ventricular function. He has a normal blood pressure on current therapy. His growth following control of hypertension is shown in Table 1, while growth in the first year after commencing treatment is summarised in Table 2.

Table 1 SDS values for height and weight
Table 2 SDS values for height and weight at presentation, 0.5 year and 1 year

Case 2: (LC)

A 10-month-old girl presented with failure to thrive and recurrent vomiting. At 14 months, her weight was 6.02 kg (<2nd percentile) and her height was 70 cm (0.4 to 2nd percentile). There was no history of ingestion of any medications. She was hypertensive, with blood pressures of 140–190/110–120 mm Hg. Cardiovascular examination was otherwise normal. Plasma electrolytes, cGFR, cortisol, thyroid function and urinary catecholamines were normal. Supine plasma renin was 56.5 nmol/l/h (normal 0.3–2.7) and aldosterone 9735 pmol/l (normal 28–445).

Echocardiography confirmed left ventricular hypertrophy. Renal ultrasound scan was normal. Left sided grade 1 vesicoureteric reflux was seen on a micturating cysto-urethrogram. A 99mTechnecium dimercaptosuccinic acid (DMSA) scan prior to therapy with an angiotensin-converting enzyme (ACE) inhibitor showed differential function to be left 65% and right 35%, with focal defects in the right lower pole and left upper and middle zones. A repeat DMSA scan 6 weeks after starting ACE inhibitor therapy showed a deterioration in function and further areas of poor perfusion. A renal angiogram was normal. A renal biopsy showed primary interstitial nephritis.

Treatment was with intravenous methylprednisolone 10 mg/kg/day for 3 days and subsequently oral prednisolone and azathioprine for 5 months. She also received labetalol, frusemide, captopril and nifedipine for blood pressure control. A repeat renal biopsy 5 months later was normal. Antihypertensive medications were gradually reduced and finally withdrawn 7 years after presentation. Her blood pressure has remained normal. Growth following control of the hypertension is shown in Table 1, while growth in the first year after commencing treatment is summarised in Table 2.

Case 3: (NW)

A 5-year-old girl presented with headache and vomiting. There was a history of vesico-ureteric reflux and recurrent urinary tract infections, and she had undergone bilateral ureteric reimplantations at the age of 7 months. She had developed a facial palsy 2 months prior to admission but the blood pressure had not been recorded. On admission her weight was 17.9 kg (9 to 25th percentile) and her height was 101 cm (2nd to 9th percentile). Her blood pressure was 190/110 mm Hg. Examination revealed cardiomegaly and an elevated jugular venous pressure. She had grade IV hypertensive retinopathy. Serum electrolyte concentrations were normal but the plasma creatinine was elevated (93 μmol/l) giving a cGFR of 45 ml/min/1.73 m2. Urinary catecholamines were normal and supine plasma renin was 3.7 nmol/l/h (normal 0.3–2.7). A chest X-ray confirmed cardiomegaly. An abdominal ultrasound scan showed a normal right kidney and a small left kidney with lower pole scarring. DMSA scan showed the relative function to be 62% on the right and 38% on the left with focal scarring of the left lower pole.

Treatment commenced with intravenous sodium nitroprusside and labetalol and subsequently the therapy was changed to enalapril, atenolol and nifedipine. She has a normal blood pressure on current therapy. Her growth following control of the hypertension is shown in Table 1, while growth in the first year after commencing treatment is summarised in Table 2.

Case 4: (SR)

A 5 and a half-year-old boy presented with epistaxis. At admission, his weight was 16.1 kg (9th percentile) and height was 109.6 cm (9th percentile). Clinical examination was normal except for the blood pressure, which was markedly elevated (180/100 mm Hg). Serum electrolytes and cGFR were normal. Ultrasound of the abdomen revealed hydronephrosis of the left kidney and an absent right kidney. A mercaptoacetyltriglycine (MAG 3) scan showed an obstruction at the pelviureteric junction and he required a pyeloplasty to relieve the obstruction. He was treated with captopril and nifedipine to control blood pressure and was later maintained on enalapril and atenolol. A repeat MAG 3 scan 3 years after surgery showed normal drainage although the hydronephrosis persisted on renal ultrasound scan. His blood pressure is normal on his current therapy of atenolol only. His growth following control of the hypertension is shown in Table 1, while growth in the first year after commencing treatment is summarised in Table 2.

Discussion

Maternal hypertension causing intrauterine growth retardation is well documented.1 The role of hypertension in postnatal growth failure has not been fully elucidated. While the cardiac, neurological and renal outcome of uncontrolled hypertension is well known, little is known of the ill effects on growth attributable to untreated hypertension only. Among the children described, case one had hypertensive heart failure which could have contributed to poor growth if it had been of sufficient duration, although it is unlikely heart failure of such severity would not have been detected previously. In all the other children there was no apparent cause for their poor growth. In cases 1, 2 and 4 the cGFR5 at presentation and throughout follow-up was normal. Case 3 had an elevated creatinine and depressed cGFR of 45 ml/min/1.73 m2 at presentation, but this improved to a creatinine value of 82 μmol/l and a cGFR of 70 ml/min/1.73 m2 at her last follow-up at 10.5 years of age. There was no evidence of marked renal impairment or any other systemic illness, their diet was not inadequate and there was no concern regarding the social and emotional environment in the families. Thus, hypertension alone was a common factor in these four children. The aetiologies of the hypertension were different in each of the children. In case 2, there was evidence of scarring on the DMSA scan while she also had interstitial nephritis. The scarring was thought to be secondary to her vesicoureteric reflux and both the conditions contributed to her hypertension, although neither were of sufficient severity to cause failure to thrive. In case 3, although the serum creatinine was elevated at presentation, her GFR increased during the course of follow up and although it did not normalise the impairment of renal function was not of sufficient severity to impair growth. Control of hypertension was achieved with antihypertensive medications and blood pressure normalised with a resultant improvement in growth. All four children were pre-pubertal and, although there was significant improvement in the first year after treatment of hypertension, the improvement continued throughout 7 years of follow up (case 2, Table 1). This again would seem to implicate hypertension as a reason for poor growth.

Hypertension was noted to cause failure to thrive and vomiting in 29% of 45 infants reported in the literature6 although the incidence of failure to thrive alone was not reported. In the same publication the incidence of growth retardation and weight loss in 600 older children was only 2.7%. It is notable that only one of the cases in our report was an infant at presentation. While describing the outcome of treatment of renovascular hypertension in a 9-month-old infant, there is mention of improvement in growth after treatment of hypertension.7 Daniels et al8 report a series of 27 patients with renal artery stenosis; 10 (37%) had growth retardation at presentation. Khalil et al9 reported failure to thrive in 34% of 23 patients with persistent hypertension. Excessive crying and failure to thrive were the most important presenting features in infants with hypertension. Renal parenchymal disease caused hypertension in 47.8% of their patients. In their study delineating the outcome of renovascular hypertension, Watson et al10 noted three of the 17 patients described who were less than 2 years of age and had associated failure to thrive were normotensive and thriving after treatment of hypertension.

The mechanisms by which hypertension can cause failure to thrive are not well documented, but anorexia, vomiting and severe cardiac failure may all contribute. Conditions such as Williams syndrome and chronic renal failure may cause hypertension and impaired growth. In other conditions such as hypertensive cardiomyopathy with cardiac failure or chronic inflammatory conditions, eg Takayasu arteritis, failure to thrive may be explained by the underlying condition. However, these explanations account for only some children with growth failure. It is well known that hyperperfusion leads to hypertrophy as is seen in Klippel-Trenauney-Weber syndrome or twin-to-twin transfusion. In hypertension, chronic vasoconstriction may lead to underperfusion of various organs and contribute to poor growth. The improvement in growth of our patients and the improvement noted in the study by Watson et al10 after hypertension had been adequately treated suggests that hypertension itself affects growth. The association between obesity and hypertension has been well documented,11 but failure to thrive secondary to hypertension has not been documented previously.

We conclude that hypertension can present with impaired growth, and that treatment of hypertension results in catch-up growth. While we accept that hypertension is an uncommon cause of failure to thrive, it is important to make the diagnosis so that appropriate investigations and treatment may be instigated. Careful measurement of blood pressure is an important aspect of the evaluation of children presenting with failure to thrive.

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Correspondence to D V Milford.

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Deshpande, P., Gilbert, R., Williams, J. et al. Hypertension: a cause of growth impairment. J Hum Hypertens 16, 363–366 (2002). https://doi.org/10.1038/sj.jhh.1001389

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Keywords

  • hypertension
  • failure to thrive
  • children

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