Management of intrahepatic cholestasis in pregnancy

1594

this patient the incubation time would seem to be more than 17 years. We are aware of two patients with infective dermatitis who died before age 20 years with what was considered to be pre-ATL, on the basis of a persistent lymphocytosis.! The case reported here therefore represents the first instance of overt ATL found in a patient with infective dermatitis. Whether infective dermatitis defines a group of individuals at increased risk of ATL will require further follow-up of large numbers of cases.

Supported by National Institutes of Health, contract

National Cancer Institute

NOI-CP-31006.

University of the West Indies, Kingston, Jamaica

BARRIE HANCHARD LOIS LAGRENADE CHRISTINE CARBERRY VALERIE FLETCHER ELAINE WILLIAMS BEVERLEY CRANSTON

National Institutes of Health,

Bethesda, Maryland

WILLIAM A. BLATTNER

Viral Epidemiology Section, National Institutes of Health,

Bethesda, Maryland 20892, USA

ANGELA MANNS

1. LaGrenade L, Hanchard B, Fletcher V, et al. Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet 1990; 336: 1345-47. 2. Sweet RD. A pattern of eczema m Jamaica. Br J Dermatol 1966; 78: 93-100. 3. Walshe MM. Infective dermatitis in Jamaican children. Br J Dermatol 1967; 79: 229-36. 4. Takatsuki K, Yamaguchi K, Kawano F, et al. Clinical aspects of adult T-cell leukemia/lymphoma (ATL): In: Miwa M, et al, eds. Retroviruses in human lymphoma/leukemia. Tokyo. Japan Scientific Society Press, 1985: 51-57. 5. Gibbs WN, Lofters W, Campbell M, et al. Non-Hodgkin’s lymphoma in Jamaica and its relationship to ATL: a study in Jamaica. Ann Intern Med 1987; 106: 331-68. 6. Hanoaka M, Sasaki M, Matsumoto H, et al. Adult T-cell leukemia: histological classification and characteristics. Acta Pathol Jpn 1979; 29: 723-38. 7. Hanchard B, Gibbs WN, Lofters W, et al. Adult T-cell leukemia/lymphoma in Jamaica. In: Blattner W, ed. Human retrovirology. New York: Raven Press, 1990: 173-83. 8. Suchi T, Lennert K, Tu L-Y, et al. Histopathology and immunohistochemistry of peripheral T-cell lymphomas: a proposal for their classification. J Clin Pathol 1987; 40: 995-1015. 9. Murphy E, Hanchard B, Figueroa JP, et al. Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with HTLV-I. Int J Cancer 1989; 43: 250-53.

training. A critical issue is whether the pregnancy will be recognised early enough. Will women always be able to understand and follow the two-stage treatment schedule and to assess whether the abortion is complete-and will they be able to seek and receive help if complications ensue (haemorrhage, incomplete abortion, uterine infection)? The implication by Norman and colleagues that oral abortifacients may compensate for the lack of access to health facilities seems naive to us. Improved access to family planning and to health care (including surgical abortion by vacuum aspiration) is perhaps a safer and more effective alternative in developing countries. Advances in drug technology do have a part to play in improving the efficiency and safety of drug-induced abortions but the central issue in developing countries is the right of women to free (or affordable), safe, and legal abortion. As in the developed world, the issues raised stretch far beyond medicine into political, cultural, and religious areas. We thank Nazneen Kanji for her

Department of Social Medicine, Federal University of Pelotas, Pelotas (RS), Brazil

WALTER FONSECA

Maternal and Child Epidemiology Unit, London School of Hygiene and Tropical Medicine

CHIZURU MISAGO

Health Policy Unit, London School of Hygiene and Tropical Medicine

NAJMI KANJI

*Present address Maternal and Child Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK

1. Fonseca W, Alencar AJC, Mota FSB, Coelho HLL. Misoprostol and congenital malformations. Lancet 1991; 338: 56. 2. Pons JC, Elefant E, Hersckorn P, Papiernik E. Development after exposure to mifepristone in early pregnancy. Lancet 1991; 338: 763. 3. Coelho HLL, Misago C, Fonseca W, Souza DSC, Araujo JML. Selling abortifacients over

the

counter

in pharmacies in Fortaleza, Brazil.

SIR,-Dr Norman and colleagues (Nov 16, p 1233) reporting on use of misoprostol plus mifepristone for terminating early pregnancy say that "an orally active prostaglandin in tablet form would be more acceptable to women and could be important in the

developing countries where access to medical facilities is limited". Their clinical results are encouraging but the small numbers of women in the three study groups call into question the extrapolation to larger populations of these findings on efficacy and safety. We question the promotion of this method as an acceptable familyplanning alternative for women in developing countries. Safety needs to be assured. Congenital malformations have been reported in five babies bom to women exposed to misoprostol early in pregnancy in unsuccessful abortion attempts.l 1 case of abnormal development of a fetus after exposure to mifepristone in early pregnancy has been reportedA deleterious effect of misoprostol plus mifepristone on the development of the fetus cannot be ruled out. Firm evidence on freedom from congenital malformations is needed before this drug can be promoted for use in pregnancy termination. In many developing countries women with unwanted pregnancies face not only poor access to medical care but also the illegality of abortion unless medically indicated. In such circumstances, it is likely that these drugs will only be available on the black-market, at a price, and proper information on drugs will not be available. For example, a study of over-the-counter selling of abortifacients in pharmacies in Fortaleza, Brazil, revealed that 80% of pharmacy personnel recommended misoprostol. However, only 7% of pharmacies mentioned the side-effects of the drug and advised women that they may need medical attention after its use.3 In developing countries, even where abortion is legal, women still face difficulties over access to medical care. Furthermore drugs are often administered by primary level health workers with limited

Lancet 1 991; 338: 247.

Management of intrahepatic cholestasis in pregnancy SIR,-lntrahepatic

Misoprostol plus mifepristone

comments.

cholestasis in pregnancy is characterised

by

jaundice) and raised maternal serum occurs in most patients during the third aminotransferases, trimester, and resolves after delivery. Although maternal outcome is invariably good, an increased fetal risk associated with cholestasis in pregnancy has been reported. No treatment improves liver function tests in cholestasis of pregnancy.2 Ursodeoxycholic acid (UDCA) is effective in the treatment of other cholestatic liver diseases such as primary biliary cirrhosis 3 A 30-year-old primigravida was referred at 34 weeks’ gestation because of cholestasis. She had a history of abnormal liver tests after oral contraceptive use. On admission she had hypertransaminasaemia, increased alkaline phosphatase, and normal serum gamma glutamyl transpeptidase. Viral markers for hepatitis A, B, and C, and for cytomegalovirus, Epstein-Barr virus, and herpesvirus were negative. Ultrasound examination revealed a morphologically normal fetus with an estimated weight between the 5th and 10th percentile for gestational age. Amniotic fluid was only slightly reduced and the non-stress test was reactive. Lecithin/ sphingomyelin ratio in amniotic fluid indicated fetal immaturity. The patient was treated with UDCA (600 mg daily in two divided doses) after informed consent. Alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, and gamma glutamyl transpeptidase were measured twice a week. Conjugated bile acids

pruritus (with

or

without

evaluated every week in serum and amniotic fluid before and the start of therapy. ALT was 438 mU/ml before treatment and rapidly decreased with treatment, reaching normal values after two weeks. Alkaline phosphatase decreased more slowly from 408 mU/ml pretreatment to 330 mU/mI on the day of delivery. Conjugated cholic acid was 22-5 umol/1 (normal < 1 lunol/1) before UDCA treatment and decreased to 2-3 lunol/1 after one week of therapy. Serum conjugated chenodeoxycolic acid was 4-9 limol/I (normal <2 umol/1) and fell to 3-3 umol/1. Serum conjugated UDCA rapidly increased to 31 umol/1 in a week. Conjugated cholic acid concentration in amniotic fluid dropped from 11-7 umol/1 to

were

ten

days after

1595

2.4 pmoill, but chenodeoxycolic acid concentrations did not change (0-4 Jl11lolfl before and 03 Jl11lolfl after therapy). UDCA concentration in amniotic fluid was 01(imol/1 after a week of treatment. The patient did not show any adverse reaction. Fetal biometric indices, evaluated every week by ultrasonography, progressively increased but remained between the 5th and 10th percentile. Fetal wellbeing was monitored daily with cardiotocography. No signs of fetal distress were seen. Amniotic fluid quantity did not change. Treatment was maintained for 20 days. At fetal maturity (37 weeks), labour was induced and a 2670 g normal baby girl was delivered with Apgar scores of 9 and 10. We suggest that UDCA treatment has a role in improving biochemical results in late onset of intrahepatic cholestasis during pregnancy.

avoiding overheating and smoking had been offered. However, these figures indicate the need to treat with caution the argument that the dramatic reduction in deaths lately reported in countries such as New Zealand and Australia is largely attributable to a preceding public health intervention programme. Scottish Cot Death Trust, Royal Hospital for Sick Children, Glasgow G3 8SJ, UK

ANGUS GIBSON HAZEL BROOKE JEAN KEELING

Respiratory syncytial virus in children’s hospitals

SIR,-Dr Stanton’s conclusion (Nov 2, p 1144) may not be justified. He shows that there was a significant reduction in sudden death in infancy (SIDS) during 1987-90 compared with the previous four years. He attributes this to parental awareness due to a "Keep Cool, Baby" campaign. However, deaths from other causes were also reduced during the same period. Had the campaign been specific in reducing SIDS deaths we would have expected deaths

SIR,-Dr Wilcox and colleagues (Oct 12, p 943) comment on the problems posed by annual epidemics of respiratory syncytial virus (RSV) infection, an experience all too familiar to paediatricians and virologists at the Children’s Hospital, Sydney. Every year more than 450 specimens-mainly nasopharyngeal aspirates, and principally from inpatients-are examined by immunofluorescence and culture. Epidemics of RSV infection occur in the colder months of every year, with very little viral activity in the first and last quarters of the year (figure). However, viral activity was in evidence during most months of 1981 and 1982.1 Epidemic peaks in the twelve years 1979-90 were in July (4), May (3), June (2), and April/May, July/August (1each), and alternation between early and later winter months, cited by Wilcox et al, was not seen. Epidemics also tended to vary in severity and scale. Alternation of major outbreaks with minor ones, as reported in Scandinavia, has not been our experienced Wilcox et al comment on the difficulties in planning for RSV epidemics because of variability in timing. The variability in peak incidence and severity that we have experienced means that we too are totally unable to predict likely epidemic patterns. Nor can we predict the proportion of infected children likely to need intensive care, which has ranged between5-7% (12/212)and 14-4% (15/104). This variation has been independent of the size of the epidemic, prompting speculation on the possible role of group A and group B

from other

RSV strains.3

Gastroenterology Unit, Istituto di Clinica Medica e Gastroenterologia, University of Bologna, 40138 Bologna, Italy, and Prenatal Pathophysiology Unit, Istituto di Clinica Ostetrica e Ginecologica, University of Bologna

GIUSEPPE MAZZELLA NICOLA RIZZO ANTONIO SALZETTA ROSSELLA IAMPIERI LUCIANO BOVICELLI ENRICO RODA

Storey GNB. Fetal outcome m obstetric cholestasis. Br J Obstet Gynaecol 1988; 95: 1137-43. 2. Shaw D, Frohlich J, Wittmann BAK, Willms M. A prospective study of 18 patients with cholestasis of pregnancy. Am J Obstet Gynecol 1982; 15: 621-25. 3 Poupon R, Chretien YK, Poupon RE, Ballet F, Calmus Y, Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987; i: 834-36. 1. Fisk NM,

Overheating and cot death

causes to

be unaffected:

Stanton’s

pleasure in the significant reduction in post-neonatal mortality Scarborough compared with the rest of the Yorkshire region (=9-1, p<0-01). However, there is no evidence that the reduction in deaths in Scarborough was different for SIDS than for reduction in deaths from other causes (p = 0-97). The association between the campaign and reduction in postneonatal mortality may not be causal, and without a control group it is difficult to evaluate such a campaign. We share

in

Department of Public Health Medicine, Barnsley District General Hospital Department

J. M. MILLER

of Public Health Medicine,

Sheffield Health Authority, Sheffield S11 8EU, UK

A. P. REDGRAVE

Reduction in sudden infant death syndrome in Scotland of sudden infant death syndrome (SIDS) in over 40% in two years with no preceding public health camnaisn aimed at reducins the risks of cot death:

SiR,-The

rate

Scotland has fallen by

*Figures in parentheses refer to first 9 months

We cannot prove that infant care practice has remained the same throughout this period and it is also possible that the decrease in SIDS might have been even greater if advice on sleep position and

RSV infections, Children’s Hospital, Sydney, 1979-90.