Fetal congenital midaortic syndrome with unilateral renal artery stenosis prenatally presenting with polyhydramnios and postpartum as hyponatremic hypertensive syndrome

Abstract

The midaortic syndrome (MAS) is a rare anomaly, characterised by narrowing of the distal aorta and its major branches. The most common symptom is severe arterial hypertension. The combination of hyponatremia, polyuria and renovascular hypertension caused by a unilateral renal artery stenosis is described as hyponatremic hypertensive syndrome. We report a case of MAS with unilateral renal artery stenosis in a preterm female neonate. A pregnant woman at 34 weeks of gestation was referred with fast growing abdominal circumference and pain. The ultrasound revealed severe polyhydramnios and fetal myocardial hypertrophy. Within the first 48 hours of the neonatal period, the diagnosis of MAS was made. We conclude that symptomatic MAS, caused by unilateral renal artery stenosis, resulting in increased renin–angiotensin–aldosterone system activity and subsequent polyuria of the non-stenotic kidney, lead to clinically significant polyhydramnios.

Background

The midaortic syndrome (MAS) is a rare congenital or acquired anomaly characterised by a narrowing of the distal thoracic and/or abdominal aorta and its major branches.¹

Symptoms (most commonly severe arterial hypertension caused by renal artery stenosis) usually present during late childhood or young adulthood.^2–4 Clinical manifestation during the newborn period is extremely rare, and cases reported so far have been characterised by neonatal death within the first weeks or months of life, either secondary to intraventricular haemorrhage or cardiac failure.^5–12 However, a few cases with better outcome in the beginning have been described.^13–16

As a result of unilateral renal artery stenosis hyponatremic hypertensive syndrome (HHS) may develop. The ischaemic kidney increases renin release causing activation of the renin–angiotensin–aldosterone system (RAAS).^17–19 This leads to hyperfiltration, pressure diuresis and loss of electrolytes from the contralateral, healthy kidney. HHS is thus characterised by severe arterial hypertension, hyponatremia and polyuria. Only a few cases of HHS in neonates have been reported, most of them caused by renal artery thrombosis following umbilical arterial catheterisation, sepsis or traumatic birth.^20–26

We report a further case of a preterm female neonate with HHS, showing severe hypertension, hyponatremia and hypokalemia within the first 24–48 hours after birth, where MAS was diagnosed postnatally. To the best of our knowledge, only two other cases with postnatal diagnosis of MAS associated with prenatal diagnosis of polyhydramnios have been described in the literature.^{6 16}

Case presentation

A 34-year-old pregnant woman (G3P1) was referred to our feto-maternal pregnancy unit at 33+3 weeks of gestation with an increase in abdominal circumference within 1 week as well as severe right flank pain. In the ultrasound scan we noticed normal maternal kidneys and a severe polyhydramnios (single deepest pocket 19 cm, amniotic fluid index 75 cm) (figure 1). The fetus was female without any morphological abnormalities with the notable exception of a myocardial hypertrophy with a thickened interventricular septum but normal contractility (figure 2). The oral glucose tolerance test and TORCH-serology screen (Toxoplasma gondii, Parvovirus B19, Treponema pallidum, Rubella, Cytomegalovirus) were normal.

Figure 1.

Prenatal ultrasound scan showing a severe polyhydramnios (single deepest pocket 19 cm, amniotic fluid index 75 cm).

Figure 2.

Prenatal ultrasound scan showing fetal myocardial hypertrophy with a thickened interventricular septum diameter of 9.42 mm (>95th centile for gestational age).

We hospitalised the patient for antenatal corticosteroid administrations for fetal lung maturation and performed an amnioreduction. Two days later an urgent caesarean section was performed due to non-reassuring fetal heart rate.

The neonate weighted 2140 g and required initial respiratory support with continuous positive airway pressure (CPAP) due to respiratory distress but was otherwise healthy. Within the first 24–48 hours of life the neonate developed increasing arterial hypertension (systolic blood pressure up to 140 mm Hg). The ultrasound and the urine analysis did not show evidence for a brain tumour or abdominal tumour. However, the plasma level of renin was significantly elevated (2394 ng/L), the echocardiogram demonstrated biventricular myocardial hypertrophy and MR-angiography revealed several short-segment and long-segment stenoses of the abdominal aorta (infrarenal stenosis up to 2 mm) with renal artery stenosis on the left, stenosis of the superior mesenteric artery and stenosis of both iliac arteries, characteristic for MAS (figure 3).

Figure 3.

MR angiography showing several short- and long-segment stenoses in the area of the abdominal aorta with left side renal artery stenosis, stenosis of the superior mesenteric artery and stenosis of both iliac arteries.

The hypertensive crisis led to escalating antihypertensive therapy, whereby the concomitant administration of six different antihypertensive drugs consisting of propanolol, clonidine, sodium nitroprusside, milrinone, furosemide and captopril was temporarily needed. The situation improved and blood pressure remained stable under triple therapy with captopril, nifedipine and spironolactone as well as intermittent support with milrinone to improve cardiac contractility.

On the first day of life the neonate was polyuric (8 mL/kg/hour), with spontaneous decrease to a normal diuresis (2 mL/kg/hour) within the first 48 hours of life.

Additionally, the neonate showed hyponatremia (minimal 129 mmol/L) on day 1 of life requiring substitution 1 day later. Over time, the sodium substitution requirements increased to high levels (maximum 20 mmol/kg/day). Furthermore, hypokalemia was diagnosed (minimal 2.6 mmol/L), requiring substitution for a much shorter time. We interpreted these symptoms in the context of HHS with secondary hyperfiltration, pressure diuresis and sodium and potassium losses from the healthy kidney caused by the activation of the RAAS. At 6 weeks of life an interventional balloon dilatation of the stenotic left renal artery (2 mm) and the distal abdominal aorta (4 mm) was performed. Postinterventional blood pressure did not change needing continuation of the antihypertensive triple therapy, which was reduced to a twofold combination within a few days. At 8 weeks of life the neonate was discharged under enalapril and nifedipine, continued sodium substitution and antiaggregation treatment with aspirin.

Outcome and follow-up

At the time of writing the newborn is 7.5 months old and developing normally. Blood pressure has remained stable under combination of enalapril and nifedipine (systolic blood pressure <100 mm Hg) and the heart function has been normal. The reduced blood flow velocitiy in the left renal artery persists on ultrasound examination and the left kidney measured smaller overall. Diuresis is normal with normal kidney function parameters. Sodium substitution was stopped in the fourth month of life. At this time, close monitoring of blood pressure, electrolytes and creatinine are planned every 4 weeks, ultrasound of the kidneys and the aorta every 2 months and echocardiography every 6 months to observe end-organ function.

In patients with MAS, failure to thrive, headache, lower extremities claudication, postprandial abdominal pain, congestive heart failure, renal insufficiency and hypertension are the most common sequelae.^1–4 MAS is correlated with significant morbidity and mortality. Without therapy, nearly half of all patients develop hypertensive encephalopathy, congestive heart failure or stroke, with mortality reaching more than 80% by the age of 40 years.^{2 3} In summary, lifelong monitoring as well as a continous therapy, possibly with need for repeated operative intervention, is essential to prevent end-organ damage and save quality of life.

Discussion

We describe a preterm female neonate with congenital MAS, severe polyhydramnios, fetal myocardial hypertrophy and HHS postnatally.

The unilateral renal artery stenosis caused by the MAS leads to ischemia of the ipsilateral kidney with increased renin release and activation of the RAAS causing hypertension aiming a better perfusion. Subsequently, the contralateral, non-stenotic kidney reacts with hyperfiltration, pressure diuresis and sodium loss. Furthermore, hypertension leads to even greater sodium and protein loss via secretion of atrial natriuretic peptide. Volume depletion and elevated angiotensin II-level stimulate release of antidiuretic hormone intensifying hyponatremia via increased water reabsorption. In the end, hypovolemia and increased renal potassium losses caused by high aldosterone-levels lead to an even greater renin excretion, resulting in a vicious circle.^{18 19 25}

We postulate that severe polyhydramnios is a possible sonographic marker of prenatally established symptomatic congenital MAS with hypertension caused by unilateral renal artery stenosis resulting in increased RAAS activity with development of polyuria of the non-stenotic kidney.

Detection of myocardial hypertrophy in prenatal ultrasound scans is an additional sign of existing arterial hypertension in the fetus.^{7 12 27}

In our case, the postulated polyuria was confirmed postnatally. We interpreted the subsequent decrease in diuresis in the context of intravascular volume depletion, which shows up first in the extrauterine circulation. It is important to substitute electrolytes and correct volume depletion in order to stabilise the systemic blood flow and avoid further renal hypoperfusion, intensifying the vicious circle.^{18 26} Adequate antihypertensive therapy should be initiated early. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are particularly suitable because they directly inhibit the over-active RAAS.^{18 19} Despite aggressive antihypertensive therapy, operative correction must be considered in many cases of HHS caused by a unilateral renal artery stenosis.^{18 24 27}

In case of MAS and HHS early diagnosis and an adequate therapy is paramount.

Although MAS is an extremely rare condition in fetuses or neonates, severe polyhydramnios, especially in combination with fetal myocardial hypertrophy, may suggest the presence of unilateral renal artery stenosis after the most common causes have been ruled out. The electrolytes should be closely monitored in order to detect possible development of HHS. HHS and secondary end-organ damage caused by hypertension are potentially curable conditions.3 12 25 27 MAS is associated with significant morbidity and mortality. It can result in refractory hypertension and often requires repeated operative treatment and multiple medications. A multidisciplinary team approach with close monitoring is essential to protect end-organ function and quality of life.

Learning points.

• Although midaortic syndrome (MAS) is an extremely rare condition, severe polyhydramnios, especially in combination with fetal myocardial hypertrophy, may suggest the presence of unilateral renal artery stenosis (eg, caused by MAS)

• In neonatal arterial hypertension resistant to standard therapeutic measures MAS with renal artery stenosis should be considered

• In unilateral renal artery stenosis (eg, caused by MAS) electrolytes should be closely monitored in order to detect possible development of hyponatremic hypertensive syndrome.