Cytomegalovirus infection in pregnancy with maternal hepatitis, neurological disease and foetal chondrodysplasia punctata

Cytomegalovirus infection in pregnancy with maternal hepatitis, neurological disease and foetal chondrodysplasia punctata

Journal of Infection (I982) 5, 93-95 CASE REPORT Cytomegalovirus infection in pregnancy with maternal hepatitis, neurological disease and foetal chon...

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Journal of Infection (I982) 5, 93-95

CASE REPORT Cytomegalovirus infection in pregnancy with maternal hepatitis, neurological disease and foetal chondrodysplasia punctata E. Walker, I. W. P i n k e r t o n a n d F. Sharp*

University Department of Infectious Diseases, Ruchill Hospital, Glasgow G2o 9NB Summary A woman in early pregnancy with active cytomegalovirus infection developed hepatitis, a psychiatric illness, and a prolonged peripheral neuropathy with some evidence of upper motor neurone damage. The foetus delivered at 20 weeks gestation showed evidence of chondrodysplasia punctata (Conradi-Hunermann type). The relationship of the infection to the woman's illness and its possible role in the aetiology of chondrodysplasia punctata are discussed.

Case report T h r e e weeks after a m o n t h ' s visit to her h o m e in Central Africa, a 24-year-old primigravida, six weeks pregnant, developed vomiting and recurrent epigastric pain. She was p r e s c r i b e d prochlorperazine and then metoclopramide. She had no previous history of serious illness or k n o w n family history of congenital abnormalities. T w o weeks later she became jaundiced. Investigations s h o w e d a normal white cell, platelet count and blood film, with no malarial parasites, spherocytes or sickling. T h r o m b o t e s t was IO per cent of normal. S e r u m bilirubin was 75 retool/l, A S T I5O i.u./1, A L T Io6o i.u./l. Hepatitis B surface antigen was not detected. Hepatitis A antibody was only of I g G class. T o x o p l a s m a and Paul Bunnell tests were negative. C M V antibody titres are described below. Over four weeks liver function r e t u r n e d to normal b u t she then became agitated, disorientated and confused. She developed horizontal nystagmus, especially to the right, ataxia of left arm, p o w e r loss in arms and legs with rapid loss of muscle bulk, absent knee jerks, ankle jerks and bilateral extensor plantar reflexes. Sensation was r e d u c e d to touch below b o t h mid thighs. Cerebrospinal fluid examination was normal. T r y p a n o s o m e s were not seen. A n electroencephalogram showed m i n o r excess of slow activity b u t no focal or definite diagnostic features. E l e c t r o m y o g r a p h y and nerve conduction studies s u p p o r t e d a diagnosis of peripheral n e u r o p a t h y b u t absent fibrillation potentials suggested i m p r o v e m e n t was likely. T o t a l I g M was raised. Other s e r u m i m m u n o g l o b u l i n s were normal. S e r u m vitamin B I2, folate, and thyroid studies were normal. Serology for syphilis and screening of s e r u m and urine for p o r p h y r i a were negative. R e p e a t e d serology for a wide range of viral and Formerly Senior Lecturer, Department of Midwifery, University of Glasgow. oi63-4453/82/o4oo93 +o4 $o2.oo/o

© I982 The British Society for the Study of Infection

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E. W A L K E R , I. W. P I N K E R T O N

AND F. S H A R P

parasitic infections showed no diagnostic titres other than a rise in c o m p l e m e n t fixation a n t i b o d y to C M V f r o m a titre of ~28 to I024. I g M specific for C M V was present. Cytomegalovirus was isolated from cervix b u t not from C S F , throat or urine. T h e patient's mental state i m p r o v e d sufficiently for the risk of foetal infection to be discussed and pregnancy was terminated at 2o weeks. C o r d blood s h o w e d I g G b u t not I g M antibody to C M V . A u t o p s y on the foetus showed no histological evidence of infection and virus was not cultured from tissues or placenta. H o w e v e r , radiographs showed chondrodysplasia punctata ( C o n r a d i - H u n e r m a n n type), with extensive abnormal calcification of cartilage (Plate I).

F u r t h e r i m p r o v e m e n t in the m o t h e r was slow. T w o years later she was slightly unstable on standing, with absent ankle jerks and diminished vibration sense in the right leg. H o w e v e r intellectual function was satisfactory and she was able to p e r f o r m m o s t normal activities. Discussion

Hepatitis in adults with cytomegalovirus infection is well d o c u m e n t e d . N e r v o u s system involvement is rare (except in the foetus) b u t encephalopathy has been r e p o r t e d in b o t h the immunologically normal and the i m m u n o s u p p r e s s e d . 1 Peripheral n e u r o p a t h y of Guillain Barr6 type occurs 2 b u t central and peripheral nervous system involvement is unusual. T h e s e features which occurred in this patient m a y have been unrelated to the C M V infection b u t extensive tests s h o w e d no other explanation. N o blood was available prior to the maternal illness so as to determine w h e t h e r the C M V infection was p r i m a r y or a reactivation. Rising antibody titres, specific I g M and g r o w t h of C M V from cervix are compatible with both. H o w e v e r the presence of specific I g M w h e n tested for b y immunofluorescence as in this case m a y be m o r e suggestive of p r i m a r y infection. T h e cause of chondrodysplasia punctata is not fully understood. Genetical influences are well established and environmental influences have been postulated. 3 D r u g s such as warfarin m a y be involved 4 and infection remains a possible aetiological factor. In this case prochlorperazine and m e t o c l o p r a m i d e were administered to the m o t h e r at a r o u n d the sixth week of pregnancy. T h e s e drugs do not so far appear to have been associated with this disease. T h e r e is evidence from this c o u n t r y that primary C M V infection is m o r e likely than reactivation to result in foetal abnormality, while the results of studies elsewhere are conflicting. 5 H o w e v e r foetal infection with C M V is usually protracted 6 and here none was d e m o n s t r a t e d I6 weeks after the maternal illness began. A transient foetal infection with foetal damage h o w e v e r remains a possibility. It has been postulated that the teratogenic effect of warfarin resulting in chondrodysplasia punctata m a y be linked to bleeding into cartilage at a critical stage in development. 7 A t h r o m b o test level of IO per cent normal was recorded during the m o t h e r ' s hepatitis w h e n she was approximately eight weeks pregnant, and this is the level r e c o m m e n d e d for satisfactory anticoagulation with warfarin. Foetal bleeding could have occurred.

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(We acknowledge with thanks the assistance of the Regional Virus L a b o r a t o r y and Bacteriology D e p a r t m e n t at Ruchill Hospital, D r J. O ' H . T o b i n , former Director, Public Health L a b o r a t o r y , Oxford and D r W. M. Fyfe, Paediatrician at Stobhill Hospital, Glasgow. Also D r A. M. Gibson, D e p a r t m e n t of Pathology, Royal Hospital for Sick Children, Glasgow for examination of the foetus and for the photographs.)

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References Phillips CA, Fanning WL, Gump DW, Phillips CF. Cytomegalovirus encephalitis in immunologically normal adults. 37,434.4 1977; 238: 2299-2300. Arnold AG, Lawrence DS, Corbitt G. Cytomegalovirus infection and the Guillain Barr6 syndrome. Postgrad Med 37, 1978; 54 (628): I I2-I I4. Spranger TW, Opitz JM, Bidder V. Heterogenecity of chondrodysplasia punctata. Humangenetik, 1971; I I : I90--212. Whitfield MF. Chondrodysplasia punctata after warfarin in early pregnancy. Arch Dis Child 198o; 55: 139-142. Grant S, Edmond E, Syme J. A prospective study of cytomegalovirus infection in pregnancy. Laboratory evidence of congenital infection following maternal primary and reactivated infection. 37 Infect 1981 ; 3 : 24-3 i. MacDonald H, Tobin J O'H. Congenital cytomegalovirus infection, a collaborative study on epidemiological, clinical and laboratory findings. Devl 34ed Child Neur 1978; 2o (4): 471-482. ShaulWL, EmeryH, HallJG. Chondrodysplasia punctata and maternal warfarin use during pregnancy. Am 37 Dis Child 1975; 129: 360-362.