Case Report Antenatal Detection of Idiopathic Arterial Calcification With Hydrops Fetalis Arpit M. Nagar, DMRD, Vijay Hanchate, MD, Ankit Tandon, MBBS, Hemangini Thakkar, MD, Nitin G. Chaubal, MD I diopathic arterial calcification of infancy, or occlusive infantile arterial calcification,1 is a rare cause of arterial calcification. This condition is inherited as an autosomal recessive pattern,2 which is almost always fatal.3 In most of the 100 cases described in the literature, the diagnosis was made at autopsy; a few cases have been reported in which an antemortem diagnosis was made on the basis of radiographic or sonographic demonstration of arterial calcification.3 The clinical characteristics are extremely variable, and respiratory distress with cardiac failure is the most common finding. Hypertension that is refractory to treatment is present in most cases. Most infants die before the age of 6 months, and very few have survived for more than 1 year.1 Mortality in this condition is caused by myocardial ischemia due to coronary artery involvement or refractory cardiac failure.3 The purpose of this report is to describe the prenatal diagnosis of idiopathic arterial calcification. Fewer than 10 cases of antenatal detection of this condition have been reported in the literature. This case is 1 of 2 cases with the earliest diagnosis of this condition so far (Table 1). Case Report Received December 23, 2002, from the Department of Radiology, King Edward Memorial Hospital, Mumbai, India. Revision requested January 2, 2003. Revised manuscript accepted for publication February 13, 2003. Address correspondence and reprint requests to Arpit M. Nagar, DMRD, Department of Radiology, King Edward Memorial Hospital, Parel, Mumbai 400012, India; e-mail: arpitnagar@hotmail.com. A 35-year-old woman, gravida 4, para 3, aborta 0, with amenorrhea for 27 weeks had enlargement of the abdomen disproportionate to her gestational age. Her obstetric history was unremarkable. Her hemoglobin level was 100 g/L; VDRL test results were negative; test results for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other acquired maternal infections were negative; and her blood group was B Rh-positive. The maternal serum calcium level, phosphorus concentration, and alkaline phosphatase concentration were within normal limits. The rest of her laboratory test results were normal. Antenatal sonography showed polyhydramnios (amniotic fluid index, 35 cm; Fig. 1), scalp edema (Fig. 2), abdominal wall edema (Fig. 3), and pleural and pericardial effusion (Figs. 4 and 5). There was © 2003 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 22:653–659, 2003 • 0278-4297/03/$3.50 Report Rosenbaum and Blumhagen4 Gestational Age, wk/Fetal Type 32/male fetus Sonographic Findings (1) Antenatal nonimmune hydrops fetalis (2) Neonatal sonography showed increased echogenicity of aorta and its branches Antenatal sonography showed polyhydramnios, pericardial effusion, hypertrophic cardiomyopathy, calcification of ascending, upper descending, and central pulmonary arteries (1) Antenatal sonography showed polyhydramnios with pericardial effusion (2) Pericardial effusion, hydrops, dilated cardiac chambers Mode of Delivery Cesarean J Ultrasound Med 22:653–659, 2003 Samon et al5 28/1 of male twins Eronen et al6 (1) 29/male fetus (2) 30/sibling of fetus 1 Levine et al7 Antenatal detection at 32/sex of fetus not reported Spear et al8 Antenatal detection (1) Nonimmune hydrops and poly(1) Cesarean of 2 siblings: (1) 32.5, hydramnios, hyperechoic arteries (2) Preterm (2) 31.5/sex of the (2) Calcification of aorta, iliac arteries, labor at siblings not reported coronary arteries, pericardial effusion 32 wk Cesarean (1) Cesarean because of fetal distress (2) Cesarean Method of Diagnosis Autopsy Findings (1) Neonatal sonography (1) Severe intimal and medial (2) Neonatal radiography hyperplasia and calcification Neonatal Outcome Congestive cardiac failure, hypertension, hematuria and death at 1 mo of age (2) Involvement of coronary arteries and renal parenchyma Neonatal chest radiogra- Not done Systemic hypertension, phy, echocardiography left ventricular hypertrophy, death at 5 mo of age (1) Autopsy (2) Echocardiography and autopsy Polyhydramnios, pericardial effusion, Antenatal death Autopsy, postnatal calcification of the ascending aorta, (exact age not fluoroscopy root of aorta, arch and descending known) aorta, coronary arteries (1) Autopsy (2) Autopsy (1) Medial calcifications in the (1) Poor ventricular ascending and descending function, cardiac aorta failure, death at (2) Intimal and medial calcifi24 d of age cations in the ascending and (2) Hydrops with descending aorta, pulmonary pleural effusion and artery, coronary arteries, and dilated cardiac chamsubendocardium bers, pericardial effusion, death after 1 h of life Deposition of calcium hydro- Intrauterine fetal death xyapatite crystals in the internal elastic lamina, focal intimal proliferation and thickening of vessel walls Deposition of calcium in the (1) Death at 34 h after internal elastic lamina and delivery media (2) Death from unremitting heart failure at 19 d of age Idiopathic Arterial Calcification With Hydrops Fetalis 654 Table 1. Antenatal Detection of Idiopathic Arterial Calcification: Reported Cases Nagar et al On the basis of these gray scale findings, a diagnosis of idiopathic arterial calcification of infancy was made. Labor was induced at 29 weeks’ gestation because of fetal distress, which was detected on obstetric Doppler sonography, and the outcome was a stillbirth. Plain radiographs of the stillborn child were taken, which showed calcification in the abdominal aorta (Fig. 11) and confirmed the diagnosis of this condition. Autopsy was not performed in this case. Discussion Figure 1. Transverse scan of the fetal abdomen showing abdominal wall edema with polyhydramnios (amniotic fluid index [AFI], 35 cm). dilatation of the right ventricle with prominence of the inferior vena cava (Fig. 6). There was echogenicity in the entire aortic wall (Fig. 7), common iliac arteries, main pulmonary artery, and bilateral renal arteries (Fig. 8). The kidneys also showed increased parenchymal echogenicity (Fig. 9). There was marked echogenicity noted in the wall of the right atrium (Fig. 10) and the main pulmonary artery. Figure 2. Transverse scan of the fetal head showing scalp edema. J Ultrasound Med 22:653–659, 2003 Idiopathic arterial calcification of infancy was first described in 1901 by Bryant and White.9 Fewer than 100 cases of this condition have been reported so far.5 This condition is characterized by patchy destruction and disruption of internal elastic lamina with deposition of calcium hydroxyapatite in this layer.4 This may be accompanied by patchy intimal proliferation and fibrosis, leading to occlusion of the lumens of the arteries and consequent ischemia. Idiopathic arterial calcification of infancy is a rare disease of unknown cause. The mechanisms of calcification postulated are altered iron metabolism,10 degeneration of elastin fibers,11 abnormal response to vascular injury,12 altered prostaglandin metabolism,13 and disorders of calcium and phosphorus metabolism.14 Figure 3. Transverse scan of the fetal abdomen showing abdominal wall edema. 655 Idiopathic Arterial Calcification With Hydrops Fetalis This condition affects both the systemic and pulmonary arteries, but it is myocardial ischemia that is the cause of death before the age of 1 year.4 There have been reports of antenatal detection of coronary7,8 and hepatic arterial15 calcification as a spectrum of this condition. Isolated case reports of this condition occurring antenatally in twins suggest a possible autosomal recessive inheritance.5 Most of these cases (≈80%) are diagnosed at autopsy,4 although this entity can be diagnosed antenatally on the basis of gray scale sonography4 or neonatal radiography.4 Other findings on antenatal sonography include polyhydramnios and signs of hydrops.5 Generalized arterial calcification in infants can be caused by hypervitaminosis D.5 Diagnosis in such patients is made after confirmation of normal serum calcium levels. However, other causes of arterial calcification in the fetus are fetal hypercalcemia and abnormal vitamin D metabolism in the fetoplacental unit, which may be related to William syndrome.16 There appear to be 2 ages for appearance of this condition5: immediately in the neonatal period and later in infancy.1,5 Recognizing this condition is difficult, because the symptoms are vague, such as lethargy, poor feeding, and respiratory distress.10,14 There is a rapid downhill clinical course, and the radiographic findings are often subtle.4 Hyperechogenicity with acoustic shadowing of the arterial walls can be noted on gray scale sonography, which is the modality of choice in this condition. If there is a family history of idiopathic arterial calcification of infancy, serial antenatal sonography is helpful in establishing the diagnosis early in pregnancy.5 Figure 5. Transverse scan of the fetal heart (FH) showing pericardial effusion. Figure 6. Transverse scan of the fetal abdomen showing an echogenic aortic wall (AO) with dilatation of the inferior vena cava (IVC). Figure 4. Transverse scan of the fetal thorax showing the fetal heart. Note the pericardial effusion with calcification of the pulmonary artery (PA). RV indicates right ventricle. 656 J Ultrasound Med 22:653–659, 2003 Nagar et al The dystrophic calcification in this condition results in decreased vessel compliance and hypertension, leading to cardiac failure and hypertrophy of the chambers.13 Fetal heart failure results in polyhydramnios, fetal hydrops, and death during the first half of the last trimester of pregnancy (as seen in our case).2,5 Premature delivery is common.6 Postnatally, the clinical findings include severe congestive cardiac failure and refractory hypertension.6 Complications of idiopathic arterial calcification of infancy include hematuria, hypertension, congestive cardiac failure, and nonimmune hydrops4 (as seen in our case). The main clinical problem in such patients is often hypertension caused by 2 mechanisms10: (1) increased vascular resistance from luminal narrowing and stiff arterial walls, which causes wide pulse pressure; and (2) renal artery stenosis, which causes increased renin levels. Renal ischemia causes the kidney to be hyperechoic on sonography. Medical treatment of cardiovascular complications is usually unsuccessful.6 Possible modalities of treatment are thyroid extract, estrogens, steroids, diphosphonates, and etidronate disodium.4 Prostaglandin E1 infusion has been successful in controlling hypertension in such patients, according to a report by Ciana et al.13 This condition is usually fatal,5 although spontaneous resolution of the calcification has been reported in 1 survivor,12 and the long-term prognosis is still unknown.4 Diphosphonates are given to decrease the calcification and to improve vascular integrity.5 This mode of treatment has been given to patients with abnormal serum calcium levels. The side effects of diphosphonate therapy outweigh its benefits in this condition.5 In conclusion, increased echogenicity of fetal vasculature should alert the sonologist of this fatal condition, which can help in early diagnosis and prompt treatment. Figure 8. Sagittal gray scale sonograms showing echogenic renal arteries on both sides. Figure 9. Sagittal scans of the fetal abdomen showing bilateral kidneys with intrarenal hyperechoic foci. Figure 7. Sagittal gray scale sonogram of the fetal chest and upper abdomen showing an echogenic wall of the entire aorta including the iliac arteries. Also note the fetal ascites. J Ultrasound Med 22:653–659, 2003 657 Idiopathic Arterial Calcification With Hydrops Fetalis Figure 10. Transverse scan of the fetal thorax showing an echogenic right atrial wall. Figure 11. Plain radiograph of the stillborn neonate showing aortic wall calcification. References 1. Saigal G. Idiopathic arterial calcification in infancy: pathology, diagnosis and treatment modalities. Indian J Pediatr 2002; 69:265–267. 7. Levine JC, Campbell J, Nadel A. Prenatal diagnosis of idiopathic infantile arterial calcification. Circulation 2001; 103:325–326. 2. Anderson KA, Burbach JA, Fenton LJ, Jaqua RA, Barlow JF. 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