- Email: [email protected]
Transient cortical blindness after coronary angiography
CORRESPONDENCE
mass, the current best marker. In the UK, we accept a poor standard of biochemical diagnosis in acute coronary syndromes compared with European and US diagnosis and management. Protocols are based on daily measurements of creatine kinase, aspartate transaminase, and lactate dehydrogenase. The limited sensitivity and specificity of these markers results in false-positive and false-negative diagnoses; this results in errors in death certificates, local and national diagnostically data, and long-term management. Creatine kinase-MB is not routinely available in the UK, despite evidence of its diagnostically superior sensitivity and specificity. Cardiac troponins represent evidence-based biochemical testing with the ability to guide therapy, predict prognosis,5 quantify damage, and confer diagnostic specificity. In an audit of 666 patients with chest pain over 3 months, we found that 47 (7%) patients had high risk of unstable angina and were missed and that 20 (3%) patients were inappropriately classified as acute myocardial infarction by WHO criteria with current biochemical markers. These errors could be avoided by cTnT measurement. Notwithstanding the psychosocial effect of inaccurate diagnosis, this group will potentially enter secondary prevention, including unnecessary long-term statin therapy. Projecting these figures to our annual caseload of 4500 patients with chest pain, what price a £4 test versus an estimated potential 10 year drug cost of £0·5 million? *P O Collinson, R Canepa-Anson, S Joseph Departments of Chemical Pathology and Cardiology, Mayday University Hospital, Thornton Heath, Surrey CR7 7YE, UK 1
2
3
4
5
Donnelly R, Millar-Craig MW, Cardiac troponins: IT upgrade for the heart. Lancet 1998; 351: 537–39. Hamm CW, Goldmann BU, Heeschen C, Kreyman G, Berger J, Meinertz T. Emergency room triage of patients by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337: 1648–53. Collinson PO, Hadcocks L, Foo AY, et al. Cardiac troponins in patients with renal dysfunction. Ann Clin Biochem (in press). Haller C, Zehelein J, Remppis A, Kübler W, Katus HA. Cardiac troponin T in patients with renal failure. J Am Coll Cardiol 1997; 29 (suppl): 234A. Lindahl B, Andren B, Ohlsson J, Venge P, Wallentin L. Risk stratification in unstable coronary artery disease: additive value of troponin determinations and pre-discharge stress tests. Eur Heart J 1997; 18: 762–70.
Sir—We agree with Richard Donnelly and Michael Millar-Craig that troponins offer several advantages over
THE LANCET • Vol 351 • May 16, 1998
conventional cardiac markers, particularly with respect to the specificity of cTnI and cTnT for myocardial cell necrosis and the near linear relation between blood concentrations of cardiac troponins and early outcome in acute coronary syndromes.2,3 However, their comment that myoglobin may be more useful for the triage of patients with chest pain in the emergency department is misleading. Although the release pattern of myoglobin makes it a sensitive early indicator of myocardial infarction, its low specificity means that it is a less valuable guide to prognosis. Patients who present with chest pain and have acute myocardial infarction ruled out by standard criteria but whose concentrations of cardiac troponin are raised have a similar short-term prognosis to those with a so-called conventional infarct. Markers such as myoglobin do not have the high specificity required to accurately identify these high-risk patients. In the emergency department, cardiac troponins may be useful in the identification of patients with minor degrees of myocardial injury who are at high risk of progressing to more extensive damage and developing serious complications. This subgroup of patients might benefit from more aggressive early intervention and certainly warrant careful observation. Troponins can also be used in the emergency department to select patients with chest pain whose risk of serious adverse cardiac events is low. Patients with chest pain for less than 12 h, without ST segment elevation on their electrocardiogram and with negative cTnT or, preferably, CTnI at least 6 h after the onset of pain can be discharged relatively safely.4 We have also confirmed that troponins add important prognostic information and can be used to facilitate safe early discharge of such low-risk patients.5 Myoglobin remains useful in the early diagnosis of infarction, particularly when efforts are made to differentiate the source—for example, by concomitant measurement of carbonic anhydrase or, in the future, use of antibodies that are selective for the skeletal muscle component. Cardiac troponins, however, offer more useful prognostic information, especially in patients without obvious evidence of myocardial infarction. *Graham Hillis, Antoinette Mangione, William Dalsey Albert Einstein Medical Center, Department of Emergency Medicine, Philadelphia, PA 19141, USA
1
2
3
4
5
Donnelly R, Millar-Craig MW. Cardiac troponins: IT upgrade for the heart. Lancet 1998; 351: 537–39. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac troponin T levels for risk stratification in acute myocardial ischaemia. N Engl J Med 1996; 335: 1333–41. Antman EM, Tanasijevic MJ, Thomson B, et al. Cardiac specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335: 1342–49. Hamm CW, Goldmann BU, Heeschen C, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337: 1648–53. Mangione A, Taggart P, Dalsey W, et al. Cardiac Acute Ischemic Rule Out (CAIRO) trial—a prospective multicenter study of a 3–12 hour diagnostic protocol for chest pain patients at low risk for myocardial infarction. Acad Emerg Med 1997; 4: 420–21.
Transient cortical blindness after coronary angiography Sir—Christian Sticherling and colleagues (Feb 21, p 570)1 report transient cortical blindness after coronary angiography. We have some observations. Although central nervous system complications of cardiac catheterisation are rare, 0·1–1% of all patients, the predominance of posterior circulation events (as opposed to anterior), has long been recognised but never fully explained. In a review of neuroophthalmological complications after this procedure, Kosmorsky and coworkers2 noted that eight of the ten patients reported had clinical or radiographic evidence of occipital lobe dysfunction and that four of these were amnestic with confusion and disorientation. One proposal to account for the posterior distribution relates to the method of catheterisation (Sones vs Judkins) with the former, antecubital approach, posited as being more likely to release embolic material into the vertebral system during guidewire positioning or catheter flushing. As in Sticherling’s case, resolution of the deficits within several days occurs in about half the patients. There is an increasingly recognised and reversible syndrome3 of headache, altered mental function, cortical blindness, and sometimes seizures associated with a predominantly posterior and largely symmetrical leucoencephalopathy on computed tomography or magnetic resonance imaging (MRI). The imaging studies are characteristic of subcortical oedema without infarction. Diverse aetiologies have been reported, including
1513
CORRESPONDENCE
eclampsia, cyclosporin neurotoxicity, and hypertensive encephalopathy. Of the 15 patients reported by Hinchey and colleagues,3 12 had abrupt increases in blood pressure and eight of these had some impairment of renal function. *Judith Hinchey, Patrick J Sweeney Department of Neurology, Cleveland Clinic Foundation, Cleveland, OH 44195,USA 1
2
3
Sticherling C, Berkefeld J, et al. Transient bilateral cortical blindness after coronary angiography. Lancet 1998; 351: 570. Kosmorsky G, Hanson MR, Tomsak RL. Neuro-ophthalmological complications of cardiac catheterisation. Neurology 1988; 38: 483–85. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.
Authors’ reply Sir—Judith Hinchey and Patrick Sweeney postulate that the predominance of the posterior distribution in cerebral complications might be influenced by the method of catheterisation. Although there are no data showing a higher incidence of cerebral embolism after cardiac catheterisation with the antecubital (Sones) than with the femoral approach (Judkins), the manipulation in the vicinity of the vertebral artery in the former technique seems to be an attractive explanation for liberation of embolic material into the vertebral system. In fact, because we visualised the left internal mammary artery graft during the procedure,1 we did angiography after computed tomography (CT) of the brain, and excluded thromboembolic events to the posterior circulation. Also, the accumulation of contrast media showed no relation to a vascular region, arguing against an embolic event as the underlying pathology. The CT result favours direct neurotoxicity of the contrast media that crossed the blood-brain barrier for unknown reasons. The widespread effect on white and grey matter in our patient also weakens the hypothesis of selective disruption of the occipital blood-brain barrier2 and gives rise to the assumption that this distribution might merely be due to prolonged supine position. Hinchey and Sweeney also raise the question of whether the symptoms seen in our patient are compatible with the recently published reversible posterior leucoencephalopathy syndrome.3 Our patient met none of the recognised risk factors, since he had no renal insufficiency, no abrupt increase in blood pressure during the study, and
1514
was not taking immunosuppressive drugs such as cyclosporin. Furthermore, we did another CT as well as an MRI scan 16 h after the initial neuroimaging. Although the CT scan showed complete clearing of the contrast media, T-2 weighted and FLAIR-MRI-sequences showed only minimum focal white matter hyperintensities and slightly dilated Virchow Robin spaces, which are regarded as normal for patients older than 50 years. The only MRI finding was a small punctuate lesion in the right ventral thalamus, probably of vascular origin. Embolic infarcts within the course of the visual system were not demonstrable. The white matter changes described by Hinchey and were much more colleagues3 pronounced and could not be found in our patient. Sequential neuroradiological imaging showed no persistent morphological changes indicative of embolic infarction or white matter changes after contrast media toxicity.
a disturbed sex ratio in offspring of diabetic mothers”. So it seemed worth extracting data from my file on this point. The table gives results from three large studies. Neither of the two smaller studies (Casson2 and Janssen3) reported a sex ratio that differs from an expected4 sex ratio of white offspring of 0·514. However, Simpson’s data4 confirm that the offspring sex ratio of male probands is normal and that the offspring sex ratio of female probands is low (2 test, p<0·005). Thus, these additional studies lend support to the differential reported by Rjasanowski and co-workers. If this differential does exist, however, its magnitude is almost certainly far less than is suggested by their data.
*Christian Sticherling, Joachim Berkefeld, Wolfgang Auch-Schwelk, Heinrich Lanfermann
2
William H James The Galton Laboratory, University College London, Wolfson House, London NW1 2HE, UK 1
Kardiologie/Nephrologie, Johann Wolfgang Goethe-Universität, 60590 Frankfurt am Main, Germany 1
2
3
2
Kamata J, Fukami K, Yoshida H, et al. Transient cortical blindness following bypass graft angiography. Angiology 1995; 46: 937–46. Kinn RM, Breisblatt WM. Cortical blindness after coronary angiography: a rare but reversible complication. Cathet Cardiovasc Diagn 1991; 22: 177–79. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leucoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.
4
Sir—We have attempted to replicate Ilona Rjasanowski and colleagues’ finding1 of a low proportion of male offspring in families with diabetic mothers. We interviewed 24 736 women and 22 535 men who were randomly selected from Copenhagen and Aarhus in Denmark. Participants in the study were aged 50–64 years at the time of interview. We compared the sex ratio in offspring of diabetics, and in subgroups defined by use of insulin and by age at onset, with the sex ratio in offspring of non-diabetics by a 2 test (table). By contrast with the results of Rjasanowski and co-workers, the sex ratio was much higher than expected (56·9 vs 50·9%, p=0·002) in offspring of diabetic
Sex ratio of offspring of diabetics Sir—Ilona Rjasanowski and colleagues (Feb 14, p 497)1 present data suggesting that a signficant excess of daughters is born to mothers (but not fathers) with insulin-dependent diabetes mellitus (IDDM). The investigators write, “to our knowledge, there have been no previoius reports of Study
Casson et al2 Janssen et al3 Simpson4
Male probands
Rjasanowski I, Klöting I, Kavacs P. Altered sex ratio in offspring of mothers with insulin-dependent diabetes mellitius. Lancet 1998; 351: 497–98. Casson IF, Clarke CA, Howard CV, et al. Outcomes of pregnancy in insulin dependent diabetic women: results of a five-year population cohort study. BMJ 1997; 315: 275–78. Janssen PA, Rothman I, Schwartz SM. Congenital malformations in newborns of women with established and gestational diabetes in Washington State 1984–91. Paed Peri Epidemiol 1996; 10: 52–63. Simpson NE. Diabetes in the families of diabetics. CMAJ 1968; 98: 427–32.
Female probands
M
F
M
F
·· ·· 2257
·· ·· 2175
170 780 2905
181 731 2970
Diagnosis of proband
IDDM Established diabetes* Diabetes
Data for Casson and colleagues2 were calculated from overall mean birthweight (3509 g), and mean birthweights of boys (3456 g) and of girls (3559 g). *The diagnosis of established diabetes differed from that of gestational diabetes, a more common disorder in Janssen’s study.3
The sexes of offspring of probands with diabetes
THE LANCET • Vol 351 • May 16, 1998
mass, the current best marker. In the UK, we accept a poor standard of biochemical diagnosis in acute coronary syndromes compared with European and US diagnosis and management. Protocols are based on daily measurements of creatine kinase, aspartate transaminase, and lactate dehydrogenase. The limited sensitivity and specificity of these markers results in false-positive and false-negative diagnoses; this results in errors in death certificates, local and national diagnostically data, and long-term management. Creatine kinase-MB is not routinely available in the UK, despite evidence of its diagnostically superior sensitivity and specificity. Cardiac troponins represent evidence-based biochemical testing with the ability to guide therapy, predict prognosis,5 quantify damage, and confer diagnostic specificity. In an audit of 666 patients with chest pain over 3 months, we found that 47 (7%) patients had high risk of unstable angina and were missed and that 20 (3%) patients were inappropriately classified as acute myocardial infarction by WHO criteria with current biochemical markers. These errors could be avoided by cTnT measurement. Notwithstanding the psychosocial effect of inaccurate diagnosis, this group will potentially enter secondary prevention, including unnecessary long-term statin therapy. Projecting these figures to our annual caseload of 4500 patients with chest pain, what price a £4 test versus an estimated potential 10 year drug cost of £0·5 million? *P O Collinson, R Canepa-Anson, S Joseph Departments of Chemical Pathology and Cardiology, Mayday University Hospital, Thornton Heath, Surrey CR7 7YE, UK 1
2
3
4
5
Donnelly R, Millar-Craig MW, Cardiac troponins: IT upgrade for the heart. Lancet 1998; 351: 537–39. Hamm CW, Goldmann BU, Heeschen C, Kreyman G, Berger J, Meinertz T. Emergency room triage of patients by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337: 1648–53. Collinson PO, Hadcocks L, Foo AY, et al. Cardiac troponins in patients with renal dysfunction. Ann Clin Biochem (in press). Haller C, Zehelein J, Remppis A, Kübler W, Katus HA. Cardiac troponin T in patients with renal failure. J Am Coll Cardiol 1997; 29 (suppl): 234A. Lindahl B, Andren B, Ohlsson J, Venge P, Wallentin L. Risk stratification in unstable coronary artery disease: additive value of troponin determinations and pre-discharge stress tests. Eur Heart J 1997; 18: 762–70.
Sir—We agree with Richard Donnelly and Michael Millar-Craig that troponins offer several advantages over
THE LANCET • Vol 351 • May 16, 1998
conventional cardiac markers, particularly with respect to the specificity of cTnI and cTnT for myocardial cell necrosis and the near linear relation between blood concentrations of cardiac troponins and early outcome in acute coronary syndromes.2,3 However, their comment that myoglobin may be more useful for the triage of patients with chest pain in the emergency department is misleading. Although the release pattern of myoglobin makes it a sensitive early indicator of myocardial infarction, its low specificity means that it is a less valuable guide to prognosis. Patients who present with chest pain and have acute myocardial infarction ruled out by standard criteria but whose concentrations of cardiac troponin are raised have a similar short-term prognosis to those with a so-called conventional infarct. Markers such as myoglobin do not have the high specificity required to accurately identify these high-risk patients. In the emergency department, cardiac troponins may be useful in the identification of patients with minor degrees of myocardial injury who are at high risk of progressing to more extensive damage and developing serious complications. This subgroup of patients might benefit from more aggressive early intervention and certainly warrant careful observation. Troponins can also be used in the emergency department to select patients with chest pain whose risk of serious adverse cardiac events is low. Patients with chest pain for less than 12 h, without ST segment elevation on their electrocardiogram and with negative cTnT or, preferably, CTnI at least 6 h after the onset of pain can be discharged relatively safely.4 We have also confirmed that troponins add important prognostic information and can be used to facilitate safe early discharge of such low-risk patients.5 Myoglobin remains useful in the early diagnosis of infarction, particularly when efforts are made to differentiate the source—for example, by concomitant measurement of carbonic anhydrase or, in the future, use of antibodies that are selective for the skeletal muscle component. Cardiac troponins, however, offer more useful prognostic information, especially in patients without obvious evidence of myocardial infarction. *Graham Hillis, Antoinette Mangione, William Dalsey Albert Einstein Medical Center, Department of Emergency Medicine, Philadelphia, PA 19141, USA
1
2
3
4
5
Donnelly R, Millar-Craig MW. Cardiac troponins: IT upgrade for the heart. Lancet 1998; 351: 537–39. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac troponin T levels for risk stratification in acute myocardial ischaemia. N Engl J Med 1996; 335: 1333–41. Antman EM, Tanasijevic MJ, Thomson B, et al. Cardiac specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335: 1342–49. Hamm CW, Goldmann BU, Heeschen C, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337: 1648–53. Mangione A, Taggart P, Dalsey W, et al. Cardiac Acute Ischemic Rule Out (CAIRO) trial—a prospective multicenter study of a 3–12 hour diagnostic protocol for chest pain patients at low risk for myocardial infarction. Acad Emerg Med 1997; 4: 420–21.
Transient cortical blindness after coronary angiography Sir—Christian Sticherling and colleagues (Feb 21, p 570)1 report transient cortical blindness after coronary angiography. We have some observations. Although central nervous system complications of cardiac catheterisation are rare, 0·1–1% of all patients, the predominance of posterior circulation events (as opposed to anterior), has long been recognised but never fully explained. In a review of neuroophthalmological complications after this procedure, Kosmorsky and coworkers2 noted that eight of the ten patients reported had clinical or radiographic evidence of occipital lobe dysfunction and that four of these were amnestic with confusion and disorientation. One proposal to account for the posterior distribution relates to the method of catheterisation (Sones vs Judkins) with the former, antecubital approach, posited as being more likely to release embolic material into the vertebral system during guidewire positioning or catheter flushing. As in Sticherling’s case, resolution of the deficits within several days occurs in about half the patients. There is an increasingly recognised and reversible syndrome3 of headache, altered mental function, cortical blindness, and sometimes seizures associated with a predominantly posterior and largely symmetrical leucoencephalopathy on computed tomography or magnetic resonance imaging (MRI). The imaging studies are characteristic of subcortical oedema without infarction. Diverse aetiologies have been reported, including
1513
CORRESPONDENCE
eclampsia, cyclosporin neurotoxicity, and hypertensive encephalopathy. Of the 15 patients reported by Hinchey and colleagues,3 12 had abrupt increases in blood pressure and eight of these had some impairment of renal function. *Judith Hinchey, Patrick J Sweeney Department of Neurology, Cleveland Clinic Foundation, Cleveland, OH 44195,USA 1
2
3
Sticherling C, Berkefeld J, et al. Transient bilateral cortical blindness after coronary angiography. Lancet 1998; 351: 570. Kosmorsky G, Hanson MR, Tomsak RL. Neuro-ophthalmological complications of cardiac catheterisation. Neurology 1988; 38: 483–85. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.
Authors’ reply Sir—Judith Hinchey and Patrick Sweeney postulate that the predominance of the posterior distribution in cerebral complications might be influenced by the method of catheterisation. Although there are no data showing a higher incidence of cerebral embolism after cardiac catheterisation with the antecubital (Sones) than with the femoral approach (Judkins), the manipulation in the vicinity of the vertebral artery in the former technique seems to be an attractive explanation for liberation of embolic material into the vertebral system. In fact, because we visualised the left internal mammary artery graft during the procedure,1 we did angiography after computed tomography (CT) of the brain, and excluded thromboembolic events to the posterior circulation. Also, the accumulation of contrast media showed no relation to a vascular region, arguing against an embolic event as the underlying pathology. The CT result favours direct neurotoxicity of the contrast media that crossed the blood-brain barrier for unknown reasons. The widespread effect on white and grey matter in our patient also weakens the hypothesis of selective disruption of the occipital blood-brain barrier2 and gives rise to the assumption that this distribution might merely be due to prolonged supine position. Hinchey and Sweeney also raise the question of whether the symptoms seen in our patient are compatible with the recently published reversible posterior leucoencephalopathy syndrome.3 Our patient met none of the recognised risk factors, since he had no renal insufficiency, no abrupt increase in blood pressure during the study, and
1514
was not taking immunosuppressive drugs such as cyclosporin. Furthermore, we did another CT as well as an MRI scan 16 h after the initial neuroimaging. Although the CT scan showed complete clearing of the contrast media, T-2 weighted and FLAIR-MRI-sequences showed only minimum focal white matter hyperintensities and slightly dilated Virchow Robin spaces, which are regarded as normal for patients older than 50 years. The only MRI finding was a small punctuate lesion in the right ventral thalamus, probably of vascular origin. Embolic infarcts within the course of the visual system were not demonstrable. The white matter changes described by Hinchey and were much more colleagues3 pronounced and could not be found in our patient. Sequential neuroradiological imaging showed no persistent morphological changes indicative of embolic infarction or white matter changes after contrast media toxicity.
a disturbed sex ratio in offspring of diabetic mothers”. So it seemed worth extracting data from my file on this point. The table gives results from three large studies. Neither of the two smaller studies (Casson2 and Janssen3) reported a sex ratio that differs from an expected4 sex ratio of white offspring of 0·514. However, Simpson’s data4 confirm that the offspring sex ratio of male probands is normal and that the offspring sex ratio of female probands is low (2 test, p<0·005). Thus, these additional studies lend support to the differential reported by Rjasanowski and co-workers. If this differential does exist, however, its magnitude is almost certainly far less than is suggested by their data.
*Christian Sticherling, Joachim Berkefeld, Wolfgang Auch-Schwelk, Heinrich Lanfermann
2
William H James The Galton Laboratory, University College London, Wolfson House, London NW1 2HE, UK 1
Kardiologie/Nephrologie, Johann Wolfgang Goethe-Universität, 60590 Frankfurt am Main, Germany 1
2
3
2
Kamata J, Fukami K, Yoshida H, et al. Transient cortical blindness following bypass graft angiography. Angiology 1995; 46: 937–46. Kinn RM, Breisblatt WM. Cortical blindness after coronary angiography: a rare but reversible complication. Cathet Cardiovasc Diagn 1991; 22: 177–79. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leucoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.
4
Sir—We have attempted to replicate Ilona Rjasanowski and colleagues’ finding1 of a low proportion of male offspring in families with diabetic mothers. We interviewed 24 736 women and 22 535 men who were randomly selected from Copenhagen and Aarhus in Denmark. Participants in the study were aged 50–64 years at the time of interview. We compared the sex ratio in offspring of diabetics, and in subgroups defined by use of insulin and by age at onset, with the sex ratio in offspring of non-diabetics by a 2 test (table). By contrast with the results of Rjasanowski and co-workers, the sex ratio was much higher than expected (56·9 vs 50·9%, p=0·002) in offspring of diabetic
Sex ratio of offspring of diabetics Sir—Ilona Rjasanowski and colleagues (Feb 14, p 497)1 present data suggesting that a signficant excess of daughters is born to mothers (but not fathers) with insulin-dependent diabetes mellitus (IDDM). The investigators write, “to our knowledge, there have been no previoius reports of Study
Casson et al2 Janssen et al3 Simpson4
Male probands
Rjasanowski I, Klöting I, Kavacs P. Altered sex ratio in offspring of mothers with insulin-dependent diabetes mellitius. Lancet 1998; 351: 497–98. Casson IF, Clarke CA, Howard CV, et al. Outcomes of pregnancy in insulin dependent diabetic women: results of a five-year population cohort study. BMJ 1997; 315: 275–78. Janssen PA, Rothman I, Schwartz SM. Congenital malformations in newborns of women with established and gestational diabetes in Washington State 1984–91. Paed Peri Epidemiol 1996; 10: 52–63. Simpson NE. Diabetes in the families of diabetics. CMAJ 1968; 98: 427–32.
Female probands
M
F
M
F
·· ·· 2257
·· ·· 2175
170 780 2905
181 731 2970
Diagnosis of proband
IDDM Established diabetes* Diabetes
Data for Casson and colleagues2 were calculated from overall mean birthweight (3509 g), and mean birthweights of boys (3456 g) and of girls (3559 g). *The diagnosis of established diabetes differed from that of gestational diabetes, a more common disorder in Janssen’s study.3
The sexes of offspring of probands with diabetes
THE LANCET • Vol 351 • May 16, 1998