I seek a clarification on the following issues.

1. What should be the clinical and laboratory workup for a severely growth retarded neonate with hepatosplenomegaly, peri-ventricular calcification, hydrocephalous, congenital cataract, persistent hyperbilirubi-nemia, and thrombocytopenia? Maternal IgM ELISA for TORCH group of agents were negative in the third trimester and on the 6th Day post partum; baby’s titer on day 1, day 6 and day 30 of age were also negative. Viral cultures for CMV were negative from blood, CSF, and urine. Liver biopsy and bone-marrow biopsy were non-contributory.

2. What is the sensitivity of ELISA for IgM anti-CMV antibodies and for viral cultures for CMV?

3. Given the low positivity of ELISA test for IgM antibodies against CMV(1), can a diagnosis of congenital CMV infection be made on clinical criteria alone despite there being a number of common clinical features between various longitudinally transmitted viral and protozoal infections.

4. What are the causes of congenital intracranial calcification in a periventricular distribution?

Devendra Mishra,
163, Sahyog Apartments,
Mayur Vihar Phase I,
Delhi 110 091, India.

Reference

1. Abraham M, Abraham P, Jana AK, Kuruvilla KA, Cherian T, Moses PD, et al. Serology in congenital infections: Experience in selected symptomatic infants. Indian Pediatr 1999; 36: 697-700.

Reply

Physicians faced with a newborn infant having signs and symptoms of perinatal infection must consider a multitude of diseases. In 1967, Alford stated, "Neonatal diagnoses of infections acquired in utero, natally and postnatally are inherently difficult"(1). Three decades later this assertion is still true, as in the case described: repeated serological evaluation for TORCH infection in the mother (antenatally and postnatally) and in the neonate was inconclusive.

During the newborn period the constellation of hepatosplenomegaly, petechiae and direct hyperbilirubinemia, with or without pneumo-nitis, microcephaly and ocular and hematologi-cal abnormalities that characterize cytomegalic inclusion disease (CID) is common to several entities. These include congenital rubella syn-drome, toxoplasmosis, syphilis, neonatal herpes simplex virus (HSV) infection and, less likely, hepatitis B and varicella zoster virus infections(2). The differential diagnosis also consists of bacterial sepsis and metabolic disorders like galactosemia and tyrosinemia.

A clinical work up involves a detailed systemic examination with particular attention paid to detect neurological, cardiovascular, ophthalmic and genito-urinary abnormalities. In the presence of periventricular calcification with negative TORCH serology and viral cultures, rarer disorders should be considered such as a recently described automsomal recessive congenital intrauterine infection-like syndrome of microcephaly, intracranial calcification and CNS disease(3,4). This condition closely mimics TORCH infections. Thus, on the basis of clinical findings, a reasonable clinical suspicion of congenital infection can be made, yet a definitive diagnosis requires laboratory evidence.

It is also known that infections may co-exist in the same patient. Hence a laboratory work up for the differential diagnoses must be thorough. Apart from routine hematological tests, meta-bolic evaluation, and screening for bacterial, viral and protozoal infections, X-ray of the long bones, ultrasonography of brain and abdomen and echocardiography are warranted.

The sensitivity of Abbott EIA for IgM anti-CMV antibody (compared to IFA and other commercially available EIA) is 97.8% and its specificity is 98.8%. However, there is only a limited role for CMV IgM testing as the sole method of diagnosis of CMV congenital infection. This is due to conditions that result in false positivity (with blood transfusion, presence of rheumatoid factor) and those that result in false negativity (infection late in the third trimester of pregnancy).

The sensitivity for viral cultures for CMV is in excess of 95% if two or three serial cultures are taken within the first two weeks of life. Urine and saliva are the samples of choice for CMV culture in suspected congenital infection - these detect >95% of infected infants(5,6). Conventional culture consists of inoculation into tube cultures of fibroblast cells. Shell vial culture is the more recent method and the DEAFF test (detection of early antigen fluorescent foci) allows rapid availability of results in 72 hours, whereas a conventional culture may take days to weeks.

The radiological picture of periventricular calcification may be seen in infections caused by CMV, Toxoplasma, rubella and HSV, tuberous sclerosis, ventriculitis, periventricular leukomalacia with calcification, and the autosomal recessive congential intrauterine infection like syndrome.

Kurien Anil Kuruvilla,
Senior Lecturer, Neonatology Unit,
Department of Pediatrics,
Christian Medical College and Hospital,
Vellore 632 002, Tamilnadu.
E-mail: [email protected].

References

1. Alford CA, Schaefer J, Blankenship WJ. A correlative immunologic, microbiologic, and clinical approach to the diagnosis of acute and chronic infections in newborn infants. N Engl J Med 1967; 277: 437-440.

2. Stagno S. Cytomegalovirus. In: Infectious Diseases of the Fetus and Newborn Infant, 4th edn. Eds. Remington JS, Klein JO. Philadelphia, W.B. Saunders, 1995, p 342.

3. Reardon W, Hockey A, Silberstein P. Autosomal recessive congenital intra-uterine infection-like syndrome of microcephaly, intracranial calcifica-tion and CNS disease. Am J Med Genet 1994; 52: 58-65.

4. al-Dabbous R, Sabry MA, Farah S, al-Awadi SA, Simeonov S, Farag TI. The autosomal recessive congenital intra-uterine infection-like syndrome of microcephaly, intracranial calcification and CNS disease. Clin Dysmorphol 1998; 7: 127-130.

5. Lennett DA, Melnick JL, Jahrling PB. Clinical Virology: Introduction to Methods. In: Manual of Clinical Microbiology, 3rd edn. Eds. Lennette EH, Balows A, Hausler WJ, Truant JP. Washington DC, American Society for Micro-biology, 1980; pp 760-771.

6. Britt WJ, Alford CA. Cytomegalovirus. In: Field’s virology Vol. 2, 3rd edn. Eds. Fields BN, Knipe DM, Howley PM. Philadelphia, Lippincott-Raven, 1996; pp 2393-2523.