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When amniotic fluid cells do not grow
Thus it should be possible to prevent a substantial number of hospital admissions and reduce mortality by using helicobacter eradication therapy for all known ulcers associated with the organism. The final possible intervention is withdrawal of all NSAIDs, which is an unrealistic suggestion. However, there is increasing evidence that such drugs are not all the same and that the risks of bleeding from ulcer associated with some could be reduced substantially by changing to another-eg, ibuprofen.6,7 An alternative therapeutic change would be to paracetamol, which provides equally good analgesia in
reported .2,13 ’
many
patients.8
The Kaiser Permanente study is welcome because it could stimulate the reappraisal of practice in other centres. I believe that assessment of means of preventing bleeding ulcers is a more sensible strategy than the fine tuning of management guidelines once the event has occurred. R P Walt Department of Medicine, Birmingham Heartlands Hospital, Birmingham, UK 1
2
3
4
5 6
7
8
Rockall TA, Logan RFA, Devlin HB, Northfield TC. Incidence and mortality of acute upper gastrointestinal bleeding (UGIB) in the UK. Gut 1994; 35 (suppl 5): S47 (abstr). Jensen DM, Cheng S, Kovacs TOG, et al. A controlled study of ranitidine for the prevention of recurrent hemorrhage from duodenal ulcer. N Engl J Med 1994; 330: 382-86. Penston JG, Wormsley KG. Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease. Aliment Pharmacol Ther 1992; 6: 629-45. Powell KU, Bell GD, Bolton GH, et al. Helicobacter pylori eradication in patients with peptic ulcer disease: clinical consequences and financial implications. Q J Med 1994; 87: 283-90. Labenz J, Borsch G. Role of Helicobacter pylori eradication in the prevention of peptic ulcer bleeding relapse. Digestion 1994; 55: 19-23. Langman MJS, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-78. Garcia Rodrigues LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal antiinflammatory drugs. Lancet 1994; 343: 769-72. March L, Irwig L, Schwartz J, Simpson J, Chock C, Brooks P. n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ 1994; 309: 1041-45.
When amniotic fluid cells do not grow See page 96 In this issue Persutte and Lenke report that amniotic fluid samples from aneuploid fetuses have a relatively high risk of culture failure; this finding has important implications for prenatal diagnosis. In developed countries, most of the 5% of pregnant women offered amniocentesis or chorionic villus sampling for fetal karyotyping have low risks of having a child with a major chromosomal abnormality. For women who are over 35, or have abnormal serum biochemical screening profiles, or have had a child with a mutant chromosome abnormality, the average risk is 1-2%, which represents a three to four fold increase over the population risk of about 0-5%. Those with increased risks are offered fetal karyotyping, usually by amniocentesis. Some of these cultures fail to grow; in Persutte and Lenke’s study, 0-7% failed. Fetal aneuploidy was found in 4 of 32 cases (2 trisomy 21, 1 trisomy 13, and 1 mosaic tetrasomy 12p); a further 7 babies had intrauterine or postnatal death or major congenital abnormalities. We now need to establish risks from a larger more detailed series. Why should amniotic fluid cell growth failure be related to fetal aneuploidy? The risks are probably linked with the
78
for failure; samples from pregnancies complicated by polyhydramnios, oligohydramnios, structural anomalies of the upper gastrointestinal or urogenital tract, or impending death usually have low viable cell numbers.’ Pallister-Killian syndrome (mosaic tetrasomy 12p) is associated with polyhydramnios and low viable cell numbers, whereas in trisomy 13 major urogenital anomalies are usually present, leading to oligohydramnios reason
1
and altered viable cell numbers. Theories about the two cases of trisomy 21 would have to include duodenal or oesophageal atresia, renal anomalies, or impending fetal demise and thus low viable cell counts. What is the relevance of these findings? For the obstetrician, gaining information about fetal abnormalities when there is still an opportunity for intervention is important for patient care and for implementing the public health aspects of screening policies, and has medicolegal implications too. For the patient, amniocentesis can cause extreme anxiety, because of fears about the normality of the baby and the risk of miscarriage. Risk of loss after sampling is about 1 in 100. The need for a second test at a later stage of gestation, with a higher chance of finding a fetal abnormality, is even more stressful and carries an additional risk of miscarriage; these concerns have to be balanced against the likelihood of detecting a chromosomal disorder. How should cases of culture failure be managed? Are there subsets of patients with increased risks for fetal aneuploidy or adverse pregnancy outcome? If they can be identified, strategies for safe rapid karyotyping at advanced gestations should be developed for high-risk cases. Detailed ultrasound examination would detect abnormal amniotic fluid volume, disordered fetal growth, or structural defects and these conditions have an increased risk of aneuploidy.2 Rapid karyotyping by cordocentesis might be an alternative to repeat amniocentesis for those with detectable anomalies, despite the greater risks of the procedure and the need for specialist skills. The exception is suspected PallisterKillian syndrome, where the chromosomal abnormality is expressed in fibroblastic but not lymphoid cells. Testing in pregnancy can cause extreme anxiety for parents about the baby’s normality. Although in Persutte and Lenke’s report 13% of failed samples had aneuploidy and a further 23% had adverse outcomes, most were normal. In those pregnancies where the fetus has no significant abnormalities, maternal feelings that the baby may still have some serious but undetected condition can persist long after the baby is born3 and are especially strong when testing is repeated. Progress towards safe and accurate identification of women with a high risk of aneuploidy from screening programmes must be tempered by recognition of the long-term harm that can be done to mothers whose babies are normal. C M Gosden Department of Obstetrics and Gynaecology, University of Liverpool, Liverpool, UK 1
2
3
Gosden CM, Brock DJH. Combined use of alphafetoprotein and amniotic fluid cell morphology in early prenatal diagnosis of fetal abnormalities. J Med Genet 1978; 15: 262-70. Nicolaides KH, Snijders RJM, Gosden CM, Berry C, Campbell S. Ultrasonographically detectable markers of fetal chromosomal abnormalities. Lancet 1992; 340: 704-07. Marteau TM, Kidd J, Cook R, et al. The psychological effects of false positive results in prenatal screening for fetal abnormality: a prospective study. Prenat Diagn 1992; 12: 205-14.
reported .2,13 ’
many
patients.8
The Kaiser Permanente study is welcome because it could stimulate the reappraisal of practice in other centres. I believe that assessment of means of preventing bleeding ulcers is a more sensible strategy than the fine tuning of management guidelines once the event has occurred. R P Walt Department of Medicine, Birmingham Heartlands Hospital, Birmingham, UK 1
2
3
4
5 6
7
8
Rockall TA, Logan RFA, Devlin HB, Northfield TC. Incidence and mortality of acute upper gastrointestinal bleeding (UGIB) in the UK. Gut 1994; 35 (suppl 5): S47 (abstr). Jensen DM, Cheng S, Kovacs TOG, et al. A controlled study of ranitidine for the prevention of recurrent hemorrhage from duodenal ulcer. N Engl J Med 1994; 330: 382-86. Penston JG, Wormsley KG. Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease. Aliment Pharmacol Ther 1992; 6: 629-45. Powell KU, Bell GD, Bolton GH, et al. Helicobacter pylori eradication in patients with peptic ulcer disease: clinical consequences and financial implications. Q J Med 1994; 87: 283-90. Labenz J, Borsch G. Role of Helicobacter pylori eradication in the prevention of peptic ulcer bleeding relapse. Digestion 1994; 55: 19-23. Langman MJS, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-78. Garcia Rodrigues LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal antiinflammatory drugs. Lancet 1994; 343: 769-72. March L, Irwig L, Schwartz J, Simpson J, Chock C, Brooks P. n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ 1994; 309: 1041-45.
When amniotic fluid cells do not grow See page 96 In this issue Persutte and Lenke report that amniotic fluid samples from aneuploid fetuses have a relatively high risk of culture failure; this finding has important implications for prenatal diagnosis. In developed countries, most of the 5% of pregnant women offered amniocentesis or chorionic villus sampling for fetal karyotyping have low risks of having a child with a major chromosomal abnormality. For women who are over 35, or have abnormal serum biochemical screening profiles, or have had a child with a mutant chromosome abnormality, the average risk is 1-2%, which represents a three to four fold increase over the population risk of about 0-5%. Those with increased risks are offered fetal karyotyping, usually by amniocentesis. Some of these cultures fail to grow; in Persutte and Lenke’s study, 0-7% failed. Fetal aneuploidy was found in 4 of 32 cases (2 trisomy 21, 1 trisomy 13, and 1 mosaic tetrasomy 12p); a further 7 babies had intrauterine or postnatal death or major congenital abnormalities. We now need to establish risks from a larger more detailed series. Why should amniotic fluid cell growth failure be related to fetal aneuploidy? The risks are probably linked with the
78
for failure; samples from pregnancies complicated by polyhydramnios, oligohydramnios, structural anomalies of the upper gastrointestinal or urogenital tract, or impending death usually have low viable cell numbers.’ Pallister-Killian syndrome (mosaic tetrasomy 12p) is associated with polyhydramnios and low viable cell numbers, whereas in trisomy 13 major urogenital anomalies are usually present, leading to oligohydramnios reason
1
and altered viable cell numbers. Theories about the two cases of trisomy 21 would have to include duodenal or oesophageal atresia, renal anomalies, or impending fetal demise and thus low viable cell counts. What is the relevance of these findings? For the obstetrician, gaining information about fetal abnormalities when there is still an opportunity for intervention is important for patient care and for implementing the public health aspects of screening policies, and has medicolegal implications too. For the patient, amniocentesis can cause extreme anxiety, because of fears about the normality of the baby and the risk of miscarriage. Risk of loss after sampling is about 1 in 100. The need for a second test at a later stage of gestation, with a higher chance of finding a fetal abnormality, is even more stressful and carries an additional risk of miscarriage; these concerns have to be balanced against the likelihood of detecting a chromosomal disorder. How should cases of culture failure be managed? Are there subsets of patients with increased risks for fetal aneuploidy or adverse pregnancy outcome? If they can be identified, strategies for safe rapid karyotyping at advanced gestations should be developed for high-risk cases. Detailed ultrasound examination would detect abnormal amniotic fluid volume, disordered fetal growth, or structural defects and these conditions have an increased risk of aneuploidy.2 Rapid karyotyping by cordocentesis might be an alternative to repeat amniocentesis for those with detectable anomalies, despite the greater risks of the procedure and the need for specialist skills. The exception is suspected PallisterKillian syndrome, where the chromosomal abnormality is expressed in fibroblastic but not lymphoid cells. Testing in pregnancy can cause extreme anxiety for parents about the baby’s normality. Although in Persutte and Lenke’s report 13% of failed samples had aneuploidy and a further 23% had adverse outcomes, most were normal. In those pregnancies where the fetus has no significant abnormalities, maternal feelings that the baby may still have some serious but undetected condition can persist long after the baby is born3 and are especially strong when testing is repeated. Progress towards safe and accurate identification of women with a high risk of aneuploidy from screening programmes must be tempered by recognition of the long-term harm that can be done to mothers whose babies are normal. C M Gosden Department of Obstetrics and Gynaecology, University of Liverpool, Liverpool, UK 1
2
3
Gosden CM, Brock DJH. Combined use of alphafetoprotein and amniotic fluid cell morphology in early prenatal diagnosis of fetal abnormalities. J Med Genet 1978; 15: 262-70. Nicolaides KH, Snijders RJM, Gosden CM, Berry C, Campbell S. Ultrasonographically detectable markers of fetal chromosomal abnormalities. Lancet 1992; 340: 704-07. Marteau TM, Kidd J, Cook R, et al. The psychological effects of false positive results in prenatal screening for fetal abnormality: a prospective study. Prenat Diagn 1992; 12: 205-14.