1359

CONGENITAL CYTOMEGALOVIRUS

INFECTION AFTER MATERNAL RENAL

STUDIES ON T-LYMPHOCYTE FUNCTION IN INFANT WITH CONGENITAL C.M.V. INFECTION

TRANSPLANTATION

J. P. K. MCCOLLUM † T. J. EVANS* H. VALDIMARSSON &Dag er; Departments of Pœdiatrics and Neonatal Medicine, and Immunology, Hammersmith Hospital, London W12

Congenital cytomegalovirus infection

Summary was found in an infant whose mother had a successful renal transplant and was treated with immunosuppressant therapy before and during preg-

Although so far not experiencing any untoward infections, the child had impaired T-lymphocyte function and subnormal serum-IgA. nancy.

Introduction an

transplantation continue to increasing number of the young

involved may

embark

pregnancy while receiving immunosuppressive therapy. Sixty-two of such cases were recorded in the llth Report of the Human Renal Transplant Registry 2; and Nolan et all reviewed twenty-three reported cases, adding two of their own. Whilst pregnancy may not substantially affect the maternal prognosis, there are nevertheless certain potential dangers to the fetus. We believe that this is the first time a case of congenital

women

now

on

cytomegalovirus (c.M.v.) infection has been reported in an infant born to a mother with a renal transplant. Case-report The mother, a 23-year-old English primipara, had chronic renal failure due to chronic pyelonephritis in 1966. After an 8-month period of hsemodialysis she received a Bilateral nephrectomy renal homotransplant in 1967. and pfarathyroidectomy were necessary, but subsequent She became pregnant in 1971, progress was satisfactory. and both before conception and during pregnancy she continued to take azathioprine (50 mg.) and prednisone (15 mg.) daily, in addition to methyldopa, dihydrotachysterol, and calcium supplements. Her progress was uneventful until the spontaneous onset of labour at 35 weeks’ gestation. She was delivered of a live female infant by forceps because of 2nd-stage delay. The baby cried at once; her weight (2060 g.) was less than the 10th percentile for gestational age, though her head circumference (31 cm.) was over the 25th percentile. There were several purpuric haemorrhages scattered over the face, trunk, and limbs which faded over the next few days; initial clinical examination was otherwise negative. Mild jaundice was evident from the 3rd day and persisted until the 15th day; the liver, at first felt just below the costal margin, increased in size to 2 cm. without accompanying splenomegaly, and felt firmer than normal. Probable intrauterine infection was diagnosed. The infant made steady progress, however, regained her birth-weight on the 10th day, and was discharged home on the 27th day weighing 2520 g. Initial investigations.-Platelet-count 80,000 (3 hours), 40,000 (3 days), and 100,000 c.mm. (5 days); serum-bilirubin (maximum 5th day), total 11’5 and conjugated 6’0 * Department of Child Health, Cardiff Royal Infirmary, Cardiff; &dag er; Institute of Child Health, Guilford Street, London WC1; ‡Department of Immunology, St. Mary’s Hospital Medical School, London W2.

Present addresses :

mg. per 100 ml. ; haemoglobin, white-blood-cell count, blood-urea, and serum phosphate and calcium were normal; serum IgG 620, IgA 5, IgM 18 mg. per 100 ml. cord blood. C.M.v. complement-fixation test 1/256 in the mother at 8 weeks’ gestation and 1/512, 5 days post C.M.V. partum; and 1/256 in the infant, aged 5 days. was cultured from the infant’s throat and urine on day 6,

and from the maternal cervix post partum.

THE results of renal

improve, and

* Normal range 25-55%. t Expressed as percentage of 3H-thymidine uptake by lymphocytes from age-matched control. Thymidine uptake below 45% is regarded as subnormal.

Infant’s Subsequent Progress She continued well, although more readily palpable and firm

the liver became even after discharge, and at 6 months was felt 5 cm. below the costal margin in the mid clavicular line. By 14 months the liver felt normal in size and consistency, and liver-function tests at 35 months were normal. Choroidoretinitis was never detected and at 35 months skull X-ray showed no calcification. Her developmental progress has been normal, and physical growth satisfactory-height, weight, and head circumference were on the 25th percentile at 35 months and before. c.M.v. was cultured again from the urine at 7 months c.M.v. and 25 months, but not at 11 and 18 months. complement-fixation titre was less than 1/8 at 6 months, and 1/16 at 14 months, when serum-immunoglobulins were normal, apart from a very low IgA (6 mg. per 100 ml., normal range 40-145 mg. per 100 ml.). T lymphocytes were counted and tested as previously At 9 months, the total-blood lymphocytedescribed.4 count was normal, while the number of T lymphocytes was significantly reduced and their response to phytohaemagglutinin was subnormal (see accompanying table). This was confirmed a month later, and T-lymphocyte function was still impaired at 14 months. However, at 10 months, blastoid transformation was shown to occur with C.M.v. antigen, although on skin testing the child was anergic to this antigen.

Renal

Discussion transplantation does not appear

to

impair

The transplanted kidney seems well able to sustain a normal pregnancy, and its pelvic situation only rarely leads to obstructed labour. The risks to the fetus, however, are increased.3 Premature rupture of membranes and premature labour are not uncommon; and judging by the birth-weights and gestational ages recorded, intrauterine growth may be retarded in over half the infants.3 The theoretical teratogenic risk to the embryo from the maternal immunosuppressant and other drugs does not appear to have been realised in practice. Azathioprine produced anomalies in laboratory animals, but human infants have nearly all been phenotypically normal. Three of the twenty-five babies reviewed by Nolan et al., however, demonstrated abnormalities of karyotype involving breaks, translocations, and deleted chromosomes; in one at least these changes later

fertility significantly.5

disappeared.

1360 Fetal immunosuppressant effects of the maternal drugs may be more definite. Lower et a1.6 reported hypoplasia of bone-marrow, lymphoid tissue, and adrenal glands at necropsy in the premature twins of a woman who had received a renal homograft and was taking azathioprine and prednisone throughout pregnancy. Cote et aU followed up the infant of a mother with chronic proliferative hypocomplement-

semic glomerulonephritis who was receiving the same drugs, though she had not had a transplant. The infant showed lymphopenia, a diminished thymic shadow on X-ray, and low serum IgG and IgM levels. c.M.v. was cultured from the mother’s urine 1 week after delivery and from the child’s urine at 10 weeks of age. At 1 year he seemed to have developed nor-

mally, though serum-IgA

was

low.

We report a case of proven congenital c.M.V. infection in the infant of a woman receiving immunosuppressant therapy after renal transplantation and throughout pregnancy. It is perhaps surprising that this complication has not been noted previously, since c.M.v. infection is a common complication of renal transplantation either by activation of "latent" virus triggered by immunosuppressive therapy or from expoThe complement-fixation sure after the operation.8 titres at the beginning and end of the pregnancy were not significantly different, and we must presume reactivation rather than primary infection. Hepatitis and transient purpura were the clinical features of the infant’s illness. That intrauterine infection may damage or delay the development of the immune system now seems clear from the many studies on children with congenital rubella.9 There are very few reports on c.M.v., but we demonstrated depression of humoral and cellular immunity in the first year of this child’s life. During that time she demonstrated no untoward susceptibility to infection and developed normally. However, an increased incidence of neoplasia with impairment of immunological function,* and the other potential fetal hazards we have reviewed, suggest that there should be a cautious attitude towards pregnancy in women taking immunosuppressive drugs and after 16 renal transplantation.

Hypothesis WHY ARE OVARIAN TERATOMAS BENIGN

WHILST TERATOMAS OF THE TESTIS ARE MALIGNANT ?

P. A. RILEY

P. M. SUTTON

Departments of Biochemical Pathology and Morbid Anatomy, University College Hospital Medical School, London WC1E 6JJ A mechanism is suggested to account Summary for the fact that most ovarian teratomas are benign (dermoid cysts) whereas testicular teratomas are almost always malignant. The mechanism advanced assumes that malignancy is caused by a recessive mutation, and then shows that the known facts of

germ-cell development will produce the homozygous (malignant) state in the male but the heterozygous counterpart in the female. It is proposed that the benign nature of ovarian teratomas is of this heterozygous genotype.

a

reflection

interesting paradox of tumour biology is that teratomas are virtually always malignant whereas teratomas of the ovary are almost invariably benign. We present here a hypothesis which explains this observation in terms of differences in development AN

testicular

of the testis and ovary.

We thank Mr Denis Hawldns for permission to abstract maternal details and Dr Pamela A. Davies for help and encouragement. Requests for reprints should be addressed to T. J. B. REFERENCES 1. Kountz, S. L., Belzer, F. O. Ann. Surg. 1972, 176, 509. 2. 11th Report of the Human Renal Transplant Registry. J. Am. med. Ass. 1973, 226, 1197. 3. Nolan, G. H., Sweet, R. L., Larus, R. K., Roure, C. A. Obstet. Gynec. 1974, 43, 732. 4. Valdimarsson, H., Hambleton, G., Henry, K., McConnell, I. Clin. exp. Immun. 1974, 16, 141. 5. Golby, M. Transplantation, 1970, 10, 201. 6. Lower, G. D., Stevens, L. E., Najarian, J. S.. Reemtsma, K. Am. J. Obstet. Gynec. 1971, 111, 1120. 7. Coté, C. J., Meuwissen, H. J., Pickering, R. J. J. Pediat. 1974, 85, 324. 8. Craighead, J. E., Hanshaw, J. B., Carpenter, C. B. J. Am. med. Ass. 1967, 201, 725. 9. South, M. A., Alford, C. A., in Immunologic Disorders in Infants and Children (edited by E. R. Stiehm and V. A. Fulginiti). Philadelphia, 1973. 10. Dent, P. B., Peterson, R. D. A., Good, R. A. in Immunologic Deficiency Diseases in Man (edited by D. Bergsma and R. A. Good); vol. 4, National Foundation Birth Defects Original Article Series. Baltimore, Maryland, 1968.

Fig. 1-Testicular teratoma. The

proposed stages are (I) a spermatogonium with two homologous chromosomes, one of which has undergone a mutation (x) which is replicated in the chromatids of the primary spermatocyte (II), giving rise to a secondary spermatocyte (III) which is homozygous for the mutation and escapes from normal growth control, undergoes chromosome replication (IV) and mitosis (V), giving rise to multiple tissue types (VI).

Congenital cytomegalovirus infection after maternal renal transplantation.

1359 CONGENITAL CYTOMEGALOVIRUS INFECTION AFTER MATERNAL RENAL STUDIES ON T-LYMPHOCYTE FUNCTION IN INFANT WITH CONGENITAL C.M.V. INFECTION TRANSPL...
275KB Sizes 0 Downloads 0 Views