118
excluded because of factors contraindicating anticoagulant therapy (a history of haemorrhagic diathesis or peptic ulcer disease, or, in a few cases, strong belief in the prophylactic value of aspirin). 156 patients were excluded because the referring physicians thought they required antiooagulant therapy, and this group is, of course, of particular importance in this context. We have gone through the records of all these patients: 101 were given warfarin because the physicians at one of the hospitals believed in the prophylactic value of warfarin after anterior wall myocardial infarction (n = 32) or after streptokinase therapy for myocardial infarction (n 69); other reasons were atrial fibrillation (n = 30), arterial embolism (n = 8), venous thrombosis (n = 6), valvular heart disease (n=4), and miscellaneous (n=7). The male/female ratio was 3-9 to 1 in these excluded patients and 3to 1 in our study group; the mean age was 615and 616, respectively. Of the patients excluded because of anticoagulant therapy, none had a known aPL syndrome.3 Thus, no patient populations at high risk for the end points were excluded. One might argue that the patients with anterior wall infarction and atrial fibrillation were at high risk for cerebral embolism; however, involvement of aPL in the pathogenesis of this condition is not suspected. Of the 1214 patients remaining after the exclusions, 607 were randomised to placebo and constitute our cohort. Our belief that no high-risk population has been removed is borne out by the high mortality (19-9%) and occurrence of reinfarction (20-1%) and cerebrovascular disease (7-4%) during the study period. We had measured aCEPHA and aCL in the entire cohort of 1200 patients. There was no effect of the antibodies on the end points in the warfarin group-as we found for the placebo group. Thus, the patient population studied was an unselected group of patients who had survived an AMI. Of course, our results do not exclude the possibility that high aPL values might be an independent risk factor for thrombo-embolic events in patients with other disorders--eg, patients with the aPL syndromethe existence of which we do not doubt. =
Haematological Research Laboratory, Department of Internal Medicine, Ullevål University Hospital, N 0407 Oslo, Norway
K. E. SLETNES P. SMITH M. ABDELNOOR H. ARNESEN F. WISLØFF
1. Smith
P, Amesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323: 147-52. 2. Smith P, Arnesen H. Mortality in non-consenters in a post-myocardial infarction trial. J Intern Med 1990; 228: 253-56. 3. Harris EN. Antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9.
readily auto-oxidise, generating free radicals and other compounds that disrupt cellular function and damage cell membranes. Increased intake of highly polyunsaturated fats increases the nutritional requirement for vitamin E, but by how and
much is not known. Contamination with toxic residues is also a concern. Lead and mercury in the commonly occurring methylated form are lipophilic, as are organochlorides such as DDT, and preferentially accumulate in the lipid stores of fish living in contaminated waters. These difficulties are surmountable by careful control of production conditions. Oxidation can be kept to a minimum by refrigeration, addition of anti-oxidants such as vitamin E, and the use of packaging that excludes light and air; and toxic residues are largely removed by efficient processing. However, such manoeuvres and the stringent quality control needed to ensure consumer safety add considerably to the cost of the final product. An alternative approach might be to encourage regular fish consumption in pregnant women. As Olsen et al point out, the differences between those who received and did not receive fish oil supplements were considerably reduced when individuals who habitually ate a lot of fish were compared, suggesting that the effect of fish oil on gestation length and birthweight has a limit. In the Aarhus study seven out of ten of the fish oil group had belching; unpleasant taste and nausea were also common. Despite these effects, compliance rates of 75% were achieved, which bespeaks participant motivation and researcher persuasiveness unlikely to be found outside the context of a clinical trial. Consuming fish rather than fish oil capsules might have the added benefit of displacing other saturated and n-6 fats from the diet. Since the effects of n-3 fatty acids are much affected by the total amount and proportions of other dietary fats, this might further potentiate their effects, leading to a reduction in the amount needed. Fred Hutchinson Cancer Research Center, Gastroenterology/Hepatology Section SC-111, Seattle, WA 98104, USA
ANNE TOBIN
Neuringer M, Connor WE. n-3 fatty adds in the brain and retina: evidence for their essentiality. Nutr Rev 1986; 44: 285-94. 2. Neuringer M, Connor WE, Lin DS, Baistad L, Luck F. Biochemical and functional effects of prenatal and postnatal n-3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci USA 1986; 83: 4021-25. 3. Thomgren M, Gustafson A. Effects of 11 week increase in dietary eicosapentaonoic acid on bleeding time, lipids and platelet aggregation. Lancet 1981; ii: 1190-93. 4. Goodnight SH, Harris WS, Connor WE. The effects of dietary w-3 fatty acids on platelet composition and function in man: a prospective study. Blood 1981; 58: 1.
880-85. 5.
Thomgren M, Shafi S, Born GVR Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2 production. Br J Haematol 1984; 58: 567-78.
Fish oil
supplementation
in pregnancy
Medical audit of the investigation of toxoplasmosis associated with pregnancy
SIR,-Dr Olsen and colleagues (April 25, p 1003) report evidence that
dietary fish oil supplements prolong gestation and increase birthweight. The fetus may benefit from maternal supplementation in other ways; the n-3 fatty acids abundant in fish oil are major components of neuronal and retinal tissue and may be involved in learning and visual acuity. 1;z.Studies of rhesus monkeys suggest that a supply of these fatty acids is especially important in the last trimester and first three months of life when membranes high in n-3 3 fatty acids are being formed? Several studies have examined the effect of large doses of fish or fish oil on coagulation. Modest reductions in platelet count and aggregation and lengthening of mean bleeding times by up to 50%3,4 have been reported. In one study whose participants ate a diet high in fish, prolongation of bleeding time was highly variable, ranging from 2 to 93%, and persisted for three weeks after supplementation.5 It is therefore not surprising that in the group of Danish women taking fish oil there was a trend towards increased blood loss at delivery. This trend was apparent despite the group’s very low caesarean section (< 9%) and assisted delivery rates. In other obstetrical populations with higher rates of surgical
intervention, bleeding complications could be substantially higher. If these promising findings are duplicated by other studies, fish oil might be offered to large numbers of healthy pregnant women. The safety of fish oil supplements warrants consideration. By virtue of their high degree of polyunsaturation, n- 3 fatty acids are unstable
SIR,-Increased awareness of toxoplasmosis in pregnancy has led demands for serotesting and for routine screening. However, the study of toxoplasmosis associated with pregnancy may be problematic and in 141 cases, we found that 98 (70%) received non-ideal investigation.1 Thus we introduced a programme of enhanced communication between reference centre and clinician and monitored the effect on patient’s care. All cases of acute toxoplasmosis associated with pregnancy first investigated during 1990 were included. Letters were sent to all responsible clinicians when laboratory records indicated ideal investigation had not been achieved. Further details of the case were requested in a questionnaire and educational material was provided. Reminders were sent to non-responders and a quarterly analysis of the findings was given to all participants. 130 cases of acute toxoplasmosis associated with pregnancy were studied. In addition to standard laboratory results, a further 170 letters and 60 h of administrative time were devoted to these cases. 6 cases of congenital toxoplasmosis were confirmed and 50 children were shown to be free of infection. A definite diagnosis was not made in 62 cases. A further 12 pregnancies did not proceed to term (5 spontaneous abortions, 1 intrauterine death, 6 terminations). 5 products of conception showed no histological evidence of toxoplasma infection and the parasite was not isolated from fetal to
excluded because of factors contraindicating anticoagulant therapy (a history of haemorrhagic diathesis or peptic ulcer disease, or, in a few cases, strong belief in the prophylactic value of aspirin). 156 patients were excluded because the referring physicians thought they required antiooagulant therapy, and this group is, of course, of particular importance in this context. We have gone through the records of all these patients: 101 were given warfarin because the physicians at one of the hospitals believed in the prophylactic value of warfarin after anterior wall myocardial infarction (n = 32) or after streptokinase therapy for myocardial infarction (n 69); other reasons were atrial fibrillation (n = 30), arterial embolism (n = 8), venous thrombosis (n = 6), valvular heart disease (n=4), and miscellaneous (n=7). The male/female ratio was 3-9 to 1 in these excluded patients and 3to 1 in our study group; the mean age was 615and 616, respectively. Of the patients excluded because of anticoagulant therapy, none had a known aPL syndrome.3 Thus, no patient populations at high risk for the end points were excluded. One might argue that the patients with anterior wall infarction and atrial fibrillation were at high risk for cerebral embolism; however, involvement of aPL in the pathogenesis of this condition is not suspected. Of the 1214 patients remaining after the exclusions, 607 were randomised to placebo and constitute our cohort. Our belief that no high-risk population has been removed is borne out by the high mortality (19-9%) and occurrence of reinfarction (20-1%) and cerebrovascular disease (7-4%) during the study period. We had measured aCEPHA and aCL in the entire cohort of 1200 patients. There was no effect of the antibodies on the end points in the warfarin group-as we found for the placebo group. Thus, the patient population studied was an unselected group of patients who had survived an AMI. Of course, our results do not exclude the possibility that high aPL values might be an independent risk factor for thrombo-embolic events in patients with other disorders--eg, patients with the aPL syndromethe existence of which we do not doubt. =
Haematological Research Laboratory, Department of Internal Medicine, Ullevål University Hospital, N 0407 Oslo, Norway
K. E. SLETNES P. SMITH M. ABDELNOOR H. ARNESEN F. WISLØFF
1. Smith
P, Amesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323: 147-52. 2. Smith P, Arnesen H. Mortality in non-consenters in a post-myocardial infarction trial. J Intern Med 1990; 228: 253-56. 3. Harris EN. Antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9.
readily auto-oxidise, generating free radicals and other compounds that disrupt cellular function and damage cell membranes. Increased intake of highly polyunsaturated fats increases the nutritional requirement for vitamin E, but by how and
much is not known. Contamination with toxic residues is also a concern. Lead and mercury in the commonly occurring methylated form are lipophilic, as are organochlorides such as DDT, and preferentially accumulate in the lipid stores of fish living in contaminated waters. These difficulties are surmountable by careful control of production conditions. Oxidation can be kept to a minimum by refrigeration, addition of anti-oxidants such as vitamin E, and the use of packaging that excludes light and air; and toxic residues are largely removed by efficient processing. However, such manoeuvres and the stringent quality control needed to ensure consumer safety add considerably to the cost of the final product. An alternative approach might be to encourage regular fish consumption in pregnant women. As Olsen et al point out, the differences between those who received and did not receive fish oil supplements were considerably reduced when individuals who habitually ate a lot of fish were compared, suggesting that the effect of fish oil on gestation length and birthweight has a limit. In the Aarhus study seven out of ten of the fish oil group had belching; unpleasant taste and nausea were also common. Despite these effects, compliance rates of 75% were achieved, which bespeaks participant motivation and researcher persuasiveness unlikely to be found outside the context of a clinical trial. Consuming fish rather than fish oil capsules might have the added benefit of displacing other saturated and n-6 fats from the diet. Since the effects of n-3 fatty acids are much affected by the total amount and proportions of other dietary fats, this might further potentiate their effects, leading to a reduction in the amount needed. Fred Hutchinson Cancer Research Center, Gastroenterology/Hepatology Section SC-111, Seattle, WA 98104, USA
ANNE TOBIN
Neuringer M, Connor WE. n-3 fatty adds in the brain and retina: evidence for their essentiality. Nutr Rev 1986; 44: 285-94. 2. Neuringer M, Connor WE, Lin DS, Baistad L, Luck F. Biochemical and functional effects of prenatal and postnatal n-3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci USA 1986; 83: 4021-25. 3. Thomgren M, Gustafson A. Effects of 11 week increase in dietary eicosapentaonoic acid on bleeding time, lipids and platelet aggregation. Lancet 1981; ii: 1190-93. 4. Goodnight SH, Harris WS, Connor WE. The effects of dietary w-3 fatty acids on platelet composition and function in man: a prospective study. Blood 1981; 58: 1.
880-85. 5.
Thomgren M, Shafi S, Born GVR Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2 production. Br J Haematol 1984; 58: 567-78.
Fish oil
supplementation
in pregnancy
Medical audit of the investigation of toxoplasmosis associated with pregnancy
SIR,-Dr Olsen and colleagues (April 25, p 1003) report evidence that
dietary fish oil supplements prolong gestation and increase birthweight. The fetus may benefit from maternal supplementation in other ways; the n-3 fatty acids abundant in fish oil are major components of neuronal and retinal tissue and may be involved in learning and visual acuity. 1;z.Studies of rhesus monkeys suggest that a supply of these fatty acids is especially important in the last trimester and first three months of life when membranes high in n-3 3 fatty acids are being formed? Several studies have examined the effect of large doses of fish or fish oil on coagulation. Modest reductions in platelet count and aggregation and lengthening of mean bleeding times by up to 50%3,4 have been reported. In one study whose participants ate a diet high in fish, prolongation of bleeding time was highly variable, ranging from 2 to 93%, and persisted for three weeks after supplementation.5 It is therefore not surprising that in the group of Danish women taking fish oil there was a trend towards increased blood loss at delivery. This trend was apparent despite the group’s very low caesarean section (< 9%) and assisted delivery rates. In other obstetrical populations with higher rates of surgical
intervention, bleeding complications could be substantially higher. If these promising findings are duplicated by other studies, fish oil might be offered to large numbers of healthy pregnant women. The safety of fish oil supplements warrants consideration. By virtue of their high degree of polyunsaturation, n- 3 fatty acids are unstable
SIR,-Increased awareness of toxoplasmosis in pregnancy has led demands for serotesting and for routine screening. However, the study of toxoplasmosis associated with pregnancy may be problematic and in 141 cases, we found that 98 (70%) received non-ideal investigation.1 Thus we introduced a programme of enhanced communication between reference centre and clinician and monitored the effect on patient’s care. All cases of acute toxoplasmosis associated with pregnancy first investigated during 1990 were included. Letters were sent to all responsible clinicians when laboratory records indicated ideal investigation had not been achieved. Further details of the case were requested in a questionnaire and educational material was provided. Reminders were sent to non-responders and a quarterly analysis of the findings was given to all participants. 130 cases of acute toxoplasmosis associated with pregnancy were studied. In addition to standard laboratory results, a further 170 letters and 60 h of administrative time were devoted to these cases. 6 cases of congenital toxoplasmosis were confirmed and 50 children were shown to be free of infection. A definite diagnosis was not made in 62 cases. A further 12 pregnancies did not proceed to term (5 spontaneous abortions, 1 intrauterine death, 6 terminations). 5 products of conception showed no histological evidence of toxoplasma infection and the parasite was not isolated from fetal to
