AUTHOR'S REPLY,-It is important that epileptic women who are pregnant should continue with some anticonvulsant treatment as if they do not the incidence of fetal abnormalities is higher than normal. Advice from the neurologist and obstetrician should be coordinated, and it is wise to use only one therapeutic agent, not several-on all these matters Dr Orrell and I agree. However, Dr Orrell also cites data on the risks of abnormalities of the central nervous system associated with sodium valproate. The teratogenic effects of various therapeutic regimens and their relation with background diseases is still mostly unproved. One recent review warned of the teratogenic effects of phenytoin, hydantoin, troxidone (trimethadione), primidone, ethosuximide, and carbamazepine as well as the possible risks of sodium valproate. ' No anticonvulsants can be proved to be completely free of teratogenic associations, and Dr Orrell is probably right that sodium valproate should not be given to women in early pregnancy because of its teratogenic associations. It may be possible either to reduce the dose in the first trimester or to substitute another anticonvulsant that currently is thought to be less teratogenic. I disagree with the action recommended in his letter for a woman who has been taking valproate inadvertently in early pregnancy. She does not need to have her ca fetoprotein concentration measured; this is only a screening test, and by current thinking this woman is already at higher risk of an abnormality. She needs detailed ultrasound scanning. If for some reason this is not available amniocentesis may be offered. GEOFFREY CHAMBERLAIN
Department of Obstetrics and Gynaecology, St George's Hospital Medical School, London SW17 ORE 1 Bailey L. Adverse elfects of drugs in the first trimester of pregnancv. London: Bailliere Tindall, 1986. (Clinics in Obstetrics and vntiaecology 1986;13(2).)
Rapid one step urine tests in early pregnancy SIR,-Mr J C P Kingdom and colleagues assessed the use of a sensitive urine test for human chorionic gonadotrophin for women with suspected complications of early pregnancy.' They considered that its negative predictive value of 100% meant that "junior gynaecologists in training" could make decisions on management based on its results. Use of similarly sensitive tests for urinary human chorionic gonadotrophin by junior medical staff is now becoming widespread in gynaecology units. As the authors admit, ectopic pregnancy may be associated with wide ranging serum human chorionic gonadotrophin concentrations. We would add a note of caution. We recently saw a young woman with irregular vaginal bleeding and lower abdominal pain. A sensitive test for urinary human chorionic gonadotrophin (RAMP, Monoclonal Antibodies Incorporated, California) gave a negative result. She was reviewed by a more experienced gynaecologist, who thought that the clinical impression was suggestive of ectopic pregnancy despite the negative results of the test. Diagnostic laparoscopy confirmed a leaking tubal pregnancy, which necessitated laparotomy and salpingectomy (histological examination confirmed an ectopic pregnancy). A blood sample taken preoperatively subsequently showed a serum human chorionic gonadotrophin concentration of 23 IU/l (within the range for non-pregnant women). As an ectopic pregnancy may be associated with low human chorionic gonadotrophin concentrations, although the negative predictive value may be close to 100% it will never be'absolutely 100%. Therefore the diagnosis of ectopic pregnancy
BMJ VOLUME 303
6 JULY 1991
may still need to be considered and some women assessed by a more experienced clinician or admitted for observation, or both. MALCOLM GRIFFITHS TAHIRA BATOOL PHILIP W REGINALD Department of Obstetrics and Gynaecology, Wexham Park Hospital, Slough, Berkshire SL2 4HL I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BMJ 1991;302: 1308-1 1. (1 June.)
SIR,-The one step test for detecting urinary human chorionic gonadotrophin reported by Mr J C P Kingdom and colleagues provides a useful additional investigation for patients presenting with suspected complications of early pregnancy.' Because of the consequences of failing to diagnose an ectopic pregnancy, however, the results should be interpreted with caution. Mr Kingdom and colleagues found the test's sensitivity to be 100%, but the 95% confidence interval for this sample (78 true positive results as assessed by the serum chorionic gonadotrophin concentration) is 95 4% to 100%. If the actual sensitivity was towards the bottom of this range it would be unacceptably low, with a false result in one in 20 pregnancies. It has been calculated that tests measuring serum human chorionic gonadotrophin concentration (limit of detection 25-50 IU/1) yield a false negative result in 4-8% of tubal pregnancies2 3 (the relation between blood and urinary human chorionic gonadotrophin concentrations is almost unitary4). The Clearview test (limit of detection 50 IU/1) identified all 12 patients with ectopic pregnancy, but with such a small sample the confidence interval is wide. Finally, we accept that a woman in pain with an ectopic pregnancy "may be less inclined to drink," thereby having a higher concentration of human chorionic gonadotrophin in her urine than in her serum. Many such women with abdominal pain receive intravenous fluids before urine is collected, which adversely affects the performance of a
qualitative test. J F R BARRETT S THORNTON S L BARRON
Department of Obstetrics and Gynaecology, Princess Mary Maternity Hospital, Newcastle upon Tyne NE2 3BD I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BM7 1991;302: 1308-11. (1 June.) 2 DiMarchi JM, Kosasa TS, Hale RW. What is the significance of the human chorionic gonadotrophin value in ectopic pregnancy? Obstet Gynecol 1989;74:851-5. 3 Romero R; Kadar N, Copel JA, Jeanty P, DeCherney AH, Hobbins JC. The effect of different human chorionic gonadotropin assay sensitivity on screening for ectopic pregnancy.
AmJ Obstet Gynecal 1985;153:72-4; 4 Norman RJ, Buck RH, Rom L, Joubert SM. Blood or urine measurement of human chorionic gonadotropin for detection of ectopic pregnancy? A comparative study of quantitative and qualitative methods in both fluids. Obstet Gynecol 1988;71:315-8.
SIR,-Mr J C P Kingdom and colleagues reported using a simple rapid one step urine test for human chorionic gonadotrophin in the initial evaluation of emergency gynaecological problems.' The sensitivity and reliability of these tests have both improved recognition of and simplified the management of disorders of early pregnancy. Our unit has had a policy of using such tests for the past two years. The confidence with which we can exclude pregnancy has enabled us to discharge patients with only vague or minimal signs and symptoms, who would otherwise have been
admitted for observation and to await laboratory assay of the chorionic gonadotrophin concentration. Staff in the accident and emergency department of our hospital, however, have limited access to such tests because of financial constraints and instead use cheaper, less sensitive two stage agglutination tests. Relying on such tests when initially assessing pregnant patients may result in some patients being discharged inappropriately. In three cases in the past six months (two of ectopic pregnancy and one of missed abortion) the patients were reported as being "cyesis negative" after initial assessment by the staff in the accident and emergency department. Subsequent urine testing with a Clearview test, either because of clinical suspicion or because the patient presented to the accident and emergency department again, yielded a positive result, and management was altered accordingly. The potential consequences of not making the diagnosis in such life threatening conditions make using such unreliable pregnancy test kits both dangerous and a false economy. It is also inevitable that with such sensitive tests several patients with either very early pregnancies or complete tubal abortions are exposed to surgical intervention, whereas serial estimations of chorionic gonadotrophin concentration or ultrasonography may have been more appropriate. Combining such sensitive pregnancy tests with a clinical examination and pelvic ultrasonography in an "early pregnancy diagnostic unit" should result in earlier diagnosis of complications in the first trimester and further improve their management.2 BASKY THILAGANATHAN SANJAY VYAS FRANK LAWTON Department of Obstetrics and Gynaecology,
King's College Hospital, London SE5 8RX I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BMJU 1991;302: 1308-11. (1 June.) 2 Bigrigg MA, Read MD. Management of women referred to early pregnancy assessment unit: care and cost effectiveness. BMJ 1991;302:577-9. (9 March.)
SIR,-We were interested in the article by Mr J C P Kingdom and colleagues on using a rapid one step urine test to evaluate suspected complications of early pregnancy as we changed last month to on site testing with the Clearview pregnancy test. We had previously relied on another test (Icon) performed by the on call medical laboratory scientific officer in microbiology at another hospital 5 km away. Delays in obtaining results out of hours were considerable, as was cost. We were particularly interested in Mr Kingdom and colleagues' observations about urinary concentration. A case recently seen by us is relevant to this. A 28 year old multiparous woman who was trying to conceive was referred by her general practitioner with lower abdominal pain and minor vaginal bleeding after six weeks of amenorrhoea. She had no risk factors for ectopic pregnancy. Her vital signs were all normal, and the duty senior house officer noted lower abdominal tenderness and bilateral pelvic tenderness. It was difficult to assess the pelvis adequately, partly because her general practitioner had advised her to attend with a full bladder to facilitate ultrasound scanning. A scan was reported as showing an empty uterus, no adnexal masses, and no free fluid in the pouch of Douglas. A Clearview pregnancy test gave a negative result. She was seen by the duty registrar, who confirmed the findings on clinical examination but found the tenderness to be greater on the right side. She was admitted overnight for observation. As the Clearview test was new to us another urine specimen was collected in the morning and an Icon test was requested; the result was reported as
57
Department of Obstetrics and Gynaecology, St George's Hospital Medical School, London SW17 ORE 1 Bailey L. Adverse elfects of drugs in the first trimester of pregnancv. London: Bailliere Tindall, 1986. (Clinics in Obstetrics and vntiaecology 1986;13(2).)
Rapid one step urine tests in early pregnancy SIR,-Mr J C P Kingdom and colleagues assessed the use of a sensitive urine test for human chorionic gonadotrophin for women with suspected complications of early pregnancy.' They considered that its negative predictive value of 100% meant that "junior gynaecologists in training" could make decisions on management based on its results. Use of similarly sensitive tests for urinary human chorionic gonadotrophin by junior medical staff is now becoming widespread in gynaecology units. As the authors admit, ectopic pregnancy may be associated with wide ranging serum human chorionic gonadotrophin concentrations. We would add a note of caution. We recently saw a young woman with irregular vaginal bleeding and lower abdominal pain. A sensitive test for urinary human chorionic gonadotrophin (RAMP, Monoclonal Antibodies Incorporated, California) gave a negative result. She was reviewed by a more experienced gynaecologist, who thought that the clinical impression was suggestive of ectopic pregnancy despite the negative results of the test. Diagnostic laparoscopy confirmed a leaking tubal pregnancy, which necessitated laparotomy and salpingectomy (histological examination confirmed an ectopic pregnancy). A blood sample taken preoperatively subsequently showed a serum human chorionic gonadotrophin concentration of 23 IU/l (within the range for non-pregnant women). As an ectopic pregnancy may be associated with low human chorionic gonadotrophin concentrations, although the negative predictive value may be close to 100% it will never be'absolutely 100%. Therefore the diagnosis of ectopic pregnancy
BMJ VOLUME 303
6 JULY 1991
may still need to be considered and some women assessed by a more experienced clinician or admitted for observation, or both. MALCOLM GRIFFITHS TAHIRA BATOOL PHILIP W REGINALD Department of Obstetrics and Gynaecology, Wexham Park Hospital, Slough, Berkshire SL2 4HL I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BMJ 1991;302: 1308-1 1. (1 June.)
SIR,-The one step test for detecting urinary human chorionic gonadotrophin reported by Mr J C P Kingdom and colleagues provides a useful additional investigation for patients presenting with suspected complications of early pregnancy.' Because of the consequences of failing to diagnose an ectopic pregnancy, however, the results should be interpreted with caution. Mr Kingdom and colleagues found the test's sensitivity to be 100%, but the 95% confidence interval for this sample (78 true positive results as assessed by the serum chorionic gonadotrophin concentration) is 95 4% to 100%. If the actual sensitivity was towards the bottom of this range it would be unacceptably low, with a false result in one in 20 pregnancies. It has been calculated that tests measuring serum human chorionic gonadotrophin concentration (limit of detection 25-50 IU/1) yield a false negative result in 4-8% of tubal pregnancies2 3 (the relation between blood and urinary human chorionic gonadotrophin concentrations is almost unitary4). The Clearview test (limit of detection 50 IU/1) identified all 12 patients with ectopic pregnancy, but with such a small sample the confidence interval is wide. Finally, we accept that a woman in pain with an ectopic pregnancy "may be less inclined to drink," thereby having a higher concentration of human chorionic gonadotrophin in her urine than in her serum. Many such women with abdominal pain receive intravenous fluids before urine is collected, which adversely affects the performance of a
qualitative test. J F R BARRETT S THORNTON S L BARRON
Department of Obstetrics and Gynaecology, Princess Mary Maternity Hospital, Newcastle upon Tyne NE2 3BD I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BM7 1991;302: 1308-11. (1 June.) 2 DiMarchi JM, Kosasa TS, Hale RW. What is the significance of the human chorionic gonadotrophin value in ectopic pregnancy? Obstet Gynecol 1989;74:851-5. 3 Romero R; Kadar N, Copel JA, Jeanty P, DeCherney AH, Hobbins JC. The effect of different human chorionic gonadotropin assay sensitivity on screening for ectopic pregnancy.
AmJ Obstet Gynecal 1985;153:72-4; 4 Norman RJ, Buck RH, Rom L, Joubert SM. Blood or urine measurement of human chorionic gonadotropin for detection of ectopic pregnancy? A comparative study of quantitative and qualitative methods in both fluids. Obstet Gynecol 1988;71:315-8.
SIR,-Mr J C P Kingdom and colleagues reported using a simple rapid one step urine test for human chorionic gonadotrophin in the initial evaluation of emergency gynaecological problems.' The sensitivity and reliability of these tests have both improved recognition of and simplified the management of disorders of early pregnancy. Our unit has had a policy of using such tests for the past two years. The confidence with which we can exclude pregnancy has enabled us to discharge patients with only vague or minimal signs and symptoms, who would otherwise have been
admitted for observation and to await laboratory assay of the chorionic gonadotrophin concentration. Staff in the accident and emergency department of our hospital, however, have limited access to such tests because of financial constraints and instead use cheaper, less sensitive two stage agglutination tests. Relying on such tests when initially assessing pregnant patients may result in some patients being discharged inappropriately. In three cases in the past six months (two of ectopic pregnancy and one of missed abortion) the patients were reported as being "cyesis negative" after initial assessment by the staff in the accident and emergency department. Subsequent urine testing with a Clearview test, either because of clinical suspicion or because the patient presented to the accident and emergency department again, yielded a positive result, and management was altered accordingly. The potential consequences of not making the diagnosis in such life threatening conditions make using such unreliable pregnancy test kits both dangerous and a false economy. It is also inevitable that with such sensitive tests several patients with either very early pregnancies or complete tubal abortions are exposed to surgical intervention, whereas serial estimations of chorionic gonadotrophin concentration or ultrasonography may have been more appropriate. Combining such sensitive pregnancy tests with a clinical examination and pelvic ultrasonography in an "early pregnancy diagnostic unit" should result in earlier diagnosis of complications in the first trimester and further improve their management.2 BASKY THILAGANATHAN SANJAY VYAS FRANK LAWTON Department of Obstetrics and Gynaecology,
King's College Hospital, London SE5 8RX I Kingdom JCP, Kelly T, MacLean AB, McAllister EJ. Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy. BMJU 1991;302: 1308-11. (1 June.) 2 Bigrigg MA, Read MD. Management of women referred to early pregnancy assessment unit: care and cost effectiveness. BMJ 1991;302:577-9. (9 March.)
SIR,-We were interested in the article by Mr J C P Kingdom and colleagues on using a rapid one step urine test to evaluate suspected complications of early pregnancy as we changed last month to on site testing with the Clearview pregnancy test. We had previously relied on another test (Icon) performed by the on call medical laboratory scientific officer in microbiology at another hospital 5 km away. Delays in obtaining results out of hours were considerable, as was cost. We were particularly interested in Mr Kingdom and colleagues' observations about urinary concentration. A case recently seen by us is relevant to this. A 28 year old multiparous woman who was trying to conceive was referred by her general practitioner with lower abdominal pain and minor vaginal bleeding after six weeks of amenorrhoea. She had no risk factors for ectopic pregnancy. Her vital signs were all normal, and the duty senior house officer noted lower abdominal tenderness and bilateral pelvic tenderness. It was difficult to assess the pelvis adequately, partly because her general practitioner had advised her to attend with a full bladder to facilitate ultrasound scanning. A scan was reported as showing an empty uterus, no adnexal masses, and no free fluid in the pouch of Douglas. A Clearview pregnancy test gave a negative result. She was seen by the duty registrar, who confirmed the findings on clinical examination but found the tenderness to be greater on the right side. She was admitted overnight for observation. As the Clearview test was new to us another urine specimen was collected in the morning and an Icon test was requested; the result was reported as
57
