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WEIGHT GAIN IN PRE-ECLAMPSIA
1297
Letters
to
the Editor
WEIGHT GAIN IN PRE-ECLAMPSIA SIR,-Mr. Philip Rhodes (March 31) has been taken to task by some of your correspondents for suggesting that " Neither the overall weight gain nor the rate of weight gain is a reliable guide to the future development of pre-eclampsia ". Dr. Mullins (April 7) avers that the restriction of weight gain in pregnancy is important for the prevention of obesity, if not of pre-eclampsia. Mr. Theobald (May 19) implies that the weekly weighing of antenatal patients, and the prevention of excessive gains, is a very important part of antenatal care, and that it can
do much to prevent eclampsia and severe pre-eclampsia. He also puts forward the hypothesis that pre-eclampsia is essentially a condition " due to unspecified defects which generally speaking interfere with normal placentation ". Some recent observations made in this unit may be of interest. The epidemiology of pre-eclampsia lends no support to the idea that this condition is a manifestation of malnutrition. It is and is not more common primarily a disease of primigravida:, in the poorer classes.12 Primigravidae who develop preeclampsia tend to gain more weight during pregnancy and to eat diets of higher calorie value, but there is no evidence that their diets are of lower nutritive value.34 MacGillivrayhas summarised evidence which suggests that pre-eclampsia accompanied by proteinuria as well as hypertension (diastolic blood-pressure 90 or more) represents a specific pathological " response to pregnancy; whereas " mild pre-eclampsia hypertension in late pregnancy without proteinuria-sometimes represents merely the temporary expression of an underlying hypertensive trait;" there are almost certainly two components to what is commonly called mild pre-eclampsia ". Thomson and Billewicz9 found in an epidemiological study of primigravidx who were allowed to eat to appetite, that the best overall results, in terms of pre-eclampsia, prematurity, and perinatal mortality, were obtained in women who gained an average of slightly less than 1 -0 lb. per week during the second half of pregnancy. Above this amount the incidence of preeclampsia was increased; below it, the prematurity-rate increased. In 1955, we began a controlled trial of weight regulation in primigravidae, to find out if the incidence of pre-eclampsia and prematurity could be reduced. An experimental group of 880 women were weighed at each antenatal visit and those who gained much more or much less than about 1-0 lb. weekly were referred to a dietitian who gave " corrective " advice. Even under exceptionally favourable conditions we failed to cause the low weight gainers to increase their rate of gain, and we found, as others have done (Dieckmann 1952), that it is by no means always easy effectively to reduce the food intake of women with good appetites and high rates of weight gain. That our efforts were attended by some success is shown by the fact that 21 % of women in the experimental group gained at an average rate of 1-2 lb. per week or more, compared with 38% in a control group of similar size selected at random from women attending the ordinary antenatal clinics, where no dietary advice was
given. The incidence of pre-eclampsia with proteinuria in the experimental group was 4-9%, compared with 5-4% in the controls, and the incidences of " mild pre-eclampsia were 22-5 and 21-1%, respectively. Many women in the experi"
mental group who developed pre-eclampsia did so without a rate of weight gain which had previously been high, and in some, the signs of pre-eclampsia persisted despite satisfactory control of an excessive gain of weight. Although the trial failed to demonstrate any significant effect of weight regulation 1. 2. 3. 4.
the incidence of pre-eclampsia, it did result in a considerable saving of antenatal beds. Per 100 cases of pre-eclampsia with proteinuria in the experimental group, 63 antenatal bed-days were required, compared with 92 days in the controls. For mild pre-eclampsia ", the equivalent figures were 234 and 415 bed-days. Similar savings of antenatal beds were achieved for antenatal complications other than pre-eclampsia. Although the clinicians concerned were disappointed by the lack of effect of weight regulation on the incidence and severity of preeclampsia, they feel strongly that dietetic advice is valuable from the point of view of heartburn, constipation, and oedema, quite apart from any general educative effect it may have. The saving of antenatal beds was probably not attributable to the dietary measures, but to the fact that in a small clinic run for research purposes, antenatal supervision in general was intensified. It was possible to supervise with safety as outpatients many women with incipient pre-eclampsia and other conditions, who at the much busier ordinary clinics would have been admitted to hospital as a precautionary measure. on
MacGillivray, I. J. Obstet. Gynœc. Brit. Commonw. 1961, 68, 557. Nelson, T. R. ibid. 1955, 62, 48, 58. Thomson, A. M., Billewicz, W. Z. Brit. med. J. 1957, i, 243. Thomson, A. M. Brit. J. Nutr. 1959, 13, 509.
"
In the
trial, just described, the outcome of pregnancy, of prematurity and perinatal mortality, as well as pre-eclampsia, showed no significant difference between the experimental and the control groups. We have recently studied pre-eclampsia as a cause of perinatal death. During the years 1958-60, 13 primiparm lost their babies from pre-eclampsia in the Aberdeen Maternity Hospital. In 4 of these, the immediate cause was accidental haemorrhage occurring while the mothers were under treatment in hospital for mild or moderate pre-eclampsia, and in 9 cases the baby weighed less than 4 lb. In at least half the cases the weight gain before the appearance of hypertension and albuminuria had not been excessive, and in the others the signs of pre-eclampsia had appeared before a pattern of high weight gain had been clearly in
terms
established. It might be argued that more significant results could have been obtained by more severe dietary restrictions more extensively applied. Such measures would be technically difficult. Furthermore, it must be remembered that only about one-third of all primigravida: gain weight at an average rate which appreciably exceeds 1 lb. per week, whereas more than one-third of the primigravida: who develop pre-eclampsia with proteinuria have not gained weight excessively. A sudden increase in rate of gain often occurs no earlier than the appearance of oedema or a rise in blood-pressure, and it may therefore fail to predict the latter. Weight restriction is not, therefore, a very efficient and certain method of reducing the incidence of pre-eclampsia. Again, we might have admitted all women with a slight rise of blood-pressure to hospital for prolonged rest and treatment, as happened with many of the control cases. Although the experimental group did just as well in terms of perinatal mortality as the controls under a policy of increased outpatient care, it could be argued that the same amount of hospital treatment as the control cases were given would have given better results. Examination of individual case-records in the fatal cases gives no support to this view. Since 1958, we have been studying by clinical and laboratory methods the nature of the weight gained during pregnancy, knowledge of which is important if attempts to regulate gains are to be placed on a rational basis. In a preliminary report5 it was shown that the average healthy primigravida who is allowed to eat to appetite gains about 12.5 kg., which is equivalent to about 1 lb. per week during the second half of pregnancy. The average gain in 5.
Thomson, A. M., Hytten, F. E. Proc. Nutr. Soc. 1961, 20, 76.
1298
body water in normal first pregnancies, seems to be wholly accounted for by the growth of the product of conception and the increase of maternal blood-volume, except during the last few weeks when there is a small excess (about 1.5 litres) of water not accounted for. At least some of this is probably oedema fluid. A rather large amount of the total weight gained (some 3-4 kg. at term) remains to be accounted for and is almost certainly fat. Fat is being laid down fast about mid-pregnancy; during the last few weeks, fat deposition slows down or ceases, total
while
’
accumulation accelerates. According to the preliminary findings in an analysis now being undertaken, it seems that women who are initially overweight are more prone to develop oedema and to have big babies, but such overweight women do not put on more than the average amount of weight during pregnancy. A possible explanation is that they do not tend to put on as much body fat as initially thin women. Studies of changes of body composition during the course of pregnancy may help to throw some light on what happens. What is clear at present is that the patterns vary widely in different individuals, and it would be a pity if undue dogmatism as to dietary management at antenatal clinics makes it unnecessarily difficult to study what is happening " normally " in pregnancies which are clinically normal in all respects other than gain in weight. There is no doubt that overeating is undesirable during pregnancy, as at other times. But whether the prevention of overeating helps to prevent pre-eclampsia remains doubtful, and continued research seems necessary. It would be interesting to know whether the differences in the incidence of pre-eclampsia from country to country, and even from area to area in one country, are associated with parallel differences in the amount of weight gained. And, indeed, it would be interesting to know exactly how much effect upon weight gain was achieved by the measures which have so successfully reduced the incidence of eclampsia in Sydney, Bradford, and elsewhere. The incidence of eclampsia in booked cases had fallen quite dramatically in Aberdeen, before we began to pay any attention to gains of weight, and our records do not suggest that patients were spontaneously gaining less water
weight. DUGALD BAIRD A. M. THOMSON F. E. HYTTEN.
Department of Midwifery and Gynaecology, University of Aberdeen.
NATURE OF HYPERTENSION SiR,ńThe articles by Dr. Lowe and Professor McKeown and by Dr. McPherson (May 26) rightly emphasise
the dangers of attributing irregularities in frequency distribution curves to the presence of two or more separate populations, especially where numbers are small; they also emphasise the importance of expert mathematical advice. Lowe and McKeown run into difficulties when they consider the implications of their findings. Taking their cue from mental deficiency, which it has been proposed should be divided into pathological and either subcultural or physiological types, they propose the division of essential hypertension into pathological and physiological types. I find myself in general agreement with what Lowe and McKeown have written, but I always suspect that long words are primarily for the purpose of deceptionultimately of self-deception. And this is no exception. "
process that may be expected bring untimely disability or reduce the of expectation life, and if we accept that disease is divisible into categories, then essential hypertension qualifies as a
If
we
accept that disease is
a
to
"disease" be "physiological" ? Is it not the meaning of the contrast between physiological and pathological that the former characterises health and the latter disease ? We have grown accustomed to defining a disease, and ultimately to ascribing it, to a unique and specific fault with a unique and specific cause. The difficulty about the kind of essential hypertension that Lowe and McKeown consider is that neither of these steps can be taken. The conviction is steadily growing that there is no natural dividing line between normal blood-pressure and hypertension, and to create one is to commit an artefact. No specific fault has been found. Nor seemingly is there a unique and specific cause. The genetic and environmental factors seem to be those which in different degrees affect the population at large-hence the term physiological. The fact would seem to be that there may be a form of disease that is different from that with which infection, deficiencies of specific food factors, and single-gene defects have made us familiar. In these diseases there is a specific fault, be it microbe infection or biochemical lesion. Those with the disease have it; those who have not the disease, in general, have not. This would be what Lowe and McKeown call pathological. Essential hypertension seems to be a disease of a different kind in which the fault is not of kind but of degree; the deviation is not qualitative but disease. Can
a
quantitative. Arterial pressure is one of the many biological characteristics that can be measured. It is the resultant of many
components-sympathetic tone, baroceptor reflexes, chemical composition of body fluids, secretion of endocrine glands, as well as the anatomical structure (including length) of the resistance vessels. No general biologist would ever think that arterial pressure-low or highwas likely to be the manifestation of a single gene defect; though of course because something is unlikely this does that it does not exist. The facts suggest that arterial pressure is the resultant of polygenic inheritance, which manifests itself in a tendency at all ages for children to resemble their parents, and of past experience, which presents as the rate of rise of pressure with age. If that were all, these fascinating and controversial articles in your journal would never have been written. Unfortunately, and of this there is no doubt, the higher the arterial pressure the greater the liability to vascular disease and the less the expectation of life. In this way arterial pressure impinges on disease. This relationship between the height of arterial pressure and what would seem to be its anatomical and biological consequences is an important part of the evidence that the disease is of a quantitative not a qualitative kind. The rest of the evidence, which I have reviewed in The Nature of Essential Hypertension, is in accord. I have always been greatly attracted by the unknown. When I was a student I went through a textbook of medicine picking out the diseases whose causation was not known. It was a long list. Some of these diseases have proved to be of the familiar qualitative kind. Others have not. Is it not possible that the habit of mind enforced by our instructional discipline has blinded us to the existence of another kind of disease of which the "physiological" type of essential hypertension is an example ? The fact not mean
Letters
to
the Editor
WEIGHT GAIN IN PRE-ECLAMPSIA SIR,-Mr. Philip Rhodes (March 31) has been taken to task by some of your correspondents for suggesting that " Neither the overall weight gain nor the rate of weight gain is a reliable guide to the future development of pre-eclampsia ". Dr. Mullins (April 7) avers that the restriction of weight gain in pregnancy is important for the prevention of obesity, if not of pre-eclampsia. Mr. Theobald (May 19) implies that the weekly weighing of antenatal patients, and the prevention of excessive gains, is a very important part of antenatal care, and that it can
do much to prevent eclampsia and severe pre-eclampsia. He also puts forward the hypothesis that pre-eclampsia is essentially a condition " due to unspecified defects which generally speaking interfere with normal placentation ". Some recent observations made in this unit may be of interest. The epidemiology of pre-eclampsia lends no support to the idea that this condition is a manifestation of malnutrition. It is and is not more common primarily a disease of primigravida:, in the poorer classes.12 Primigravidae who develop preeclampsia tend to gain more weight during pregnancy and to eat diets of higher calorie value, but there is no evidence that their diets are of lower nutritive value.34 MacGillivrayhas summarised evidence which suggests that pre-eclampsia accompanied by proteinuria as well as hypertension (diastolic blood-pressure 90 or more) represents a specific pathological " response to pregnancy; whereas " mild pre-eclampsia hypertension in late pregnancy without proteinuria-sometimes represents merely the temporary expression of an underlying hypertensive trait;" there are almost certainly two components to what is commonly called mild pre-eclampsia ". Thomson and Billewicz9 found in an epidemiological study of primigravidx who were allowed to eat to appetite, that the best overall results, in terms of pre-eclampsia, prematurity, and perinatal mortality, were obtained in women who gained an average of slightly less than 1 -0 lb. per week during the second half of pregnancy. Above this amount the incidence of preeclampsia was increased; below it, the prematurity-rate increased. In 1955, we began a controlled trial of weight regulation in primigravidae, to find out if the incidence of pre-eclampsia and prematurity could be reduced. An experimental group of 880 women were weighed at each antenatal visit and those who gained much more or much less than about 1-0 lb. weekly were referred to a dietitian who gave " corrective " advice. Even under exceptionally favourable conditions we failed to cause the low weight gainers to increase their rate of gain, and we found, as others have done (Dieckmann 1952), that it is by no means always easy effectively to reduce the food intake of women with good appetites and high rates of weight gain. That our efforts were attended by some success is shown by the fact that 21 % of women in the experimental group gained at an average rate of 1-2 lb. per week or more, compared with 38% in a control group of similar size selected at random from women attending the ordinary antenatal clinics, where no dietary advice was
given. The incidence of pre-eclampsia with proteinuria in the experimental group was 4-9%, compared with 5-4% in the controls, and the incidences of " mild pre-eclampsia were 22-5 and 21-1%, respectively. Many women in the experi"
mental group who developed pre-eclampsia did so without a rate of weight gain which had previously been high, and in some, the signs of pre-eclampsia persisted despite satisfactory control of an excessive gain of weight. Although the trial failed to demonstrate any significant effect of weight regulation 1. 2. 3. 4.
the incidence of pre-eclampsia, it did result in a considerable saving of antenatal beds. Per 100 cases of pre-eclampsia with proteinuria in the experimental group, 63 antenatal bed-days were required, compared with 92 days in the controls. For mild pre-eclampsia ", the equivalent figures were 234 and 415 bed-days. Similar savings of antenatal beds were achieved for antenatal complications other than pre-eclampsia. Although the clinicians concerned were disappointed by the lack of effect of weight regulation on the incidence and severity of preeclampsia, they feel strongly that dietetic advice is valuable from the point of view of heartburn, constipation, and oedema, quite apart from any general educative effect it may have. The saving of antenatal beds was probably not attributable to the dietary measures, but to the fact that in a small clinic run for research purposes, antenatal supervision in general was intensified. It was possible to supervise with safety as outpatients many women with incipient pre-eclampsia and other conditions, who at the much busier ordinary clinics would have been admitted to hospital as a precautionary measure. on
MacGillivray, I. J. Obstet. Gynœc. Brit. Commonw. 1961, 68, 557. Nelson, T. R. ibid. 1955, 62, 48, 58. Thomson, A. M., Billewicz, W. Z. Brit. med. J. 1957, i, 243. Thomson, A. M. Brit. J. Nutr. 1959, 13, 509.
"
In the
trial, just described, the outcome of pregnancy, of prematurity and perinatal mortality, as well as pre-eclampsia, showed no significant difference between the experimental and the control groups. We have recently studied pre-eclampsia as a cause of perinatal death. During the years 1958-60, 13 primiparm lost their babies from pre-eclampsia in the Aberdeen Maternity Hospital. In 4 of these, the immediate cause was accidental haemorrhage occurring while the mothers were under treatment in hospital for mild or moderate pre-eclampsia, and in 9 cases the baby weighed less than 4 lb. In at least half the cases the weight gain before the appearance of hypertension and albuminuria had not been excessive, and in the others the signs of pre-eclampsia had appeared before a pattern of high weight gain had been clearly in
terms
established. It might be argued that more significant results could have been obtained by more severe dietary restrictions more extensively applied. Such measures would be technically difficult. Furthermore, it must be remembered that only about one-third of all primigravida: gain weight at an average rate which appreciably exceeds 1 lb. per week, whereas more than one-third of the primigravida: who develop pre-eclampsia with proteinuria have not gained weight excessively. A sudden increase in rate of gain often occurs no earlier than the appearance of oedema or a rise in blood-pressure, and it may therefore fail to predict the latter. Weight restriction is not, therefore, a very efficient and certain method of reducing the incidence of pre-eclampsia. Again, we might have admitted all women with a slight rise of blood-pressure to hospital for prolonged rest and treatment, as happened with many of the control cases. Although the experimental group did just as well in terms of perinatal mortality as the controls under a policy of increased outpatient care, it could be argued that the same amount of hospital treatment as the control cases were given would have given better results. Examination of individual case-records in the fatal cases gives no support to this view. Since 1958, we have been studying by clinical and laboratory methods the nature of the weight gained during pregnancy, knowledge of which is important if attempts to regulate gains are to be placed on a rational basis. In a preliminary report5 it was shown that the average healthy primigravida who is allowed to eat to appetite gains about 12.5 kg., which is equivalent to about 1 lb. per week during the second half of pregnancy. The average gain in 5.
Thomson, A. M., Hytten, F. E. Proc. Nutr. Soc. 1961, 20, 76.
1298
body water in normal first pregnancies, seems to be wholly accounted for by the growth of the product of conception and the increase of maternal blood-volume, except during the last few weeks when there is a small excess (about 1.5 litres) of water not accounted for. At least some of this is probably oedema fluid. A rather large amount of the total weight gained (some 3-4 kg. at term) remains to be accounted for and is almost certainly fat. Fat is being laid down fast about mid-pregnancy; during the last few weeks, fat deposition slows down or ceases, total
while
’
accumulation accelerates. According to the preliminary findings in an analysis now being undertaken, it seems that women who are initially overweight are more prone to develop oedema and to have big babies, but such overweight women do not put on more than the average amount of weight during pregnancy. A possible explanation is that they do not tend to put on as much body fat as initially thin women. Studies of changes of body composition during the course of pregnancy may help to throw some light on what happens. What is clear at present is that the patterns vary widely in different individuals, and it would be a pity if undue dogmatism as to dietary management at antenatal clinics makes it unnecessarily difficult to study what is happening " normally " in pregnancies which are clinically normal in all respects other than gain in weight. There is no doubt that overeating is undesirable during pregnancy, as at other times. But whether the prevention of overeating helps to prevent pre-eclampsia remains doubtful, and continued research seems necessary. It would be interesting to know whether the differences in the incidence of pre-eclampsia from country to country, and even from area to area in one country, are associated with parallel differences in the amount of weight gained. And, indeed, it would be interesting to know exactly how much effect upon weight gain was achieved by the measures which have so successfully reduced the incidence of eclampsia in Sydney, Bradford, and elsewhere. The incidence of eclampsia in booked cases had fallen quite dramatically in Aberdeen, before we began to pay any attention to gains of weight, and our records do not suggest that patients were spontaneously gaining less water
weight. DUGALD BAIRD A. M. THOMSON F. E. HYTTEN.
Department of Midwifery and Gynaecology, University of Aberdeen.
NATURE OF HYPERTENSION SiR,ńThe articles by Dr. Lowe and Professor McKeown and by Dr. McPherson (May 26) rightly emphasise
the dangers of attributing irregularities in frequency distribution curves to the presence of two or more separate populations, especially where numbers are small; they also emphasise the importance of expert mathematical advice. Lowe and McKeown run into difficulties when they consider the implications of their findings. Taking their cue from mental deficiency, which it has been proposed should be divided into pathological and either subcultural or physiological types, they propose the division of essential hypertension into pathological and physiological types. I find myself in general agreement with what Lowe and McKeown have written, but I always suspect that long words are primarily for the purpose of deceptionultimately of self-deception. And this is no exception. "
process that may be expected bring untimely disability or reduce the of expectation life, and if we accept that disease is divisible into categories, then essential hypertension qualifies as a
If
we
accept that disease is
a
to
"disease" be "physiological" ? Is it not the meaning of the contrast between physiological and pathological that the former characterises health and the latter disease ? We have grown accustomed to defining a disease, and ultimately to ascribing it, to a unique and specific fault with a unique and specific cause. The difficulty about the kind of essential hypertension that Lowe and McKeown consider is that neither of these steps can be taken. The conviction is steadily growing that there is no natural dividing line between normal blood-pressure and hypertension, and to create one is to commit an artefact. No specific fault has been found. Nor seemingly is there a unique and specific cause. The genetic and environmental factors seem to be those which in different degrees affect the population at large-hence the term physiological. The fact would seem to be that there may be a form of disease that is different from that with which infection, deficiencies of specific food factors, and single-gene defects have made us familiar. In these diseases there is a specific fault, be it microbe infection or biochemical lesion. Those with the disease have it; those who have not the disease, in general, have not. This would be what Lowe and McKeown call pathological. Essential hypertension seems to be a disease of a different kind in which the fault is not of kind but of degree; the deviation is not qualitative but disease. Can
a
quantitative. Arterial pressure is one of the many biological characteristics that can be measured. It is the resultant of many
components-sympathetic tone, baroceptor reflexes, chemical composition of body fluids, secretion of endocrine glands, as well as the anatomical structure (including length) of the resistance vessels. No general biologist would ever think that arterial pressure-low or highwas likely to be the manifestation of a single gene defect; though of course because something is unlikely this does that it does not exist. The facts suggest that arterial pressure is the resultant of polygenic inheritance, which manifests itself in a tendency at all ages for children to resemble their parents, and of past experience, which presents as the rate of rise of pressure with age. If that were all, these fascinating and controversial articles in your journal would never have been written. Unfortunately, and of this there is no doubt, the higher the arterial pressure the greater the liability to vascular disease and the less the expectation of life. In this way arterial pressure impinges on disease. This relationship between the height of arterial pressure and what would seem to be its anatomical and biological consequences is an important part of the evidence that the disease is of a quantitative not a qualitative kind. The rest of the evidence, which I have reviewed in The Nature of Essential Hypertension, is in accord. I have always been greatly attracted by the unknown. When I was a student I went through a textbook of medicine picking out the diseases whose causation was not known. It was a long list. Some of these diseases have proved to be of the familiar qualitative kind. Others have not. Is it not possible that the habit of mind enforced by our instructional discipline has blinded us to the existence of another kind of disease of which the "physiological" type of essential hypertension is an example ? The fact not mean