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CONGENITAL MALFORMATIONS
134
make the crew understand that salt deficiency is something which anyone but a fool will take trouble to avoid. But ships with fewer than 100 people on board do not have to carry a doctor. Dr. LEITHEAD and his colleagues suggest various ways Young men are casual, and a certain foolhardiness befits seafarers. But these are poor consolations after in which the risks of these voyages could be reduced. a man has died because he did not bother to take extra But there is another that leaps to the eye. Granted that salt at meals, or thought the suggestion soft. Surely, one cannot expect to have a fully qualified medical man people who make use of scientific discoveries, and live in every vessel at sea, why should there be this immense the new kind of lives that science has made possible, difference between the medical care of 101 men, who bught to be willing to listen also to what science says must have a registered medical practitioner, and of 99 about the preservation of their health-and safety in the who need have nobody trained to advise them or attend new artificial environments ? But the necessary knowwisely to those minor illnesses which in the tropics are ledge needs to be supplied to them repeatedly and with so uncomfortably liable to become major ? Many years conviction; and, though many senior officers are inter- have now passed since the Association of Sea and Air ested, they mostly lack time for promoting preventive Port Health Authorities recommended that the smaller medicine in detail. Of course, if the ship has a doctor, ships should each carry a sickbay steward. We must he will be able to overcome irrelevant prejudices and ask why this is not yet done.
On each voyage, acclimatisation must be achieved almost afresh, and there is a danger period, of a week or more, until the body has learnt to conserve salt by reducing the salt content of the sweat.
Annotations
ORIGINS
OF SOCIAL PSYCHIATRY
IT is commonly believed that a real increase in mental breakdown is following on the raised tempo of modem life and our rapid cultural changes. Unfortunately the statistics are still so fallible, and the boundaries of mental health and illness so hazy, that fact can scarcely be distinguished from fallacy-let alone from fantasy. Some aspects of the " horizontal " approach, as it were, to culture and mental illness by G. M. Carstairs in his anthropological work were lately reviewed in these columns ’-; and on July 8 at the Institute of Psychiatry, London, Prof. George Rosen, of Columbia University, " a vertical" or longitudinal view. presented
In a scholarly address he pointed out that the concept of sociocultural determination in mental illness is not by any means new. Benjamin Rush studied the effects of the American Revolution on the participants: being an ardent revolutionary himself, he noticed among his ranks an increase in health and happiness, the cure of hysterical disorders among the women, and blessings granted to previously infertile marriages. Among those still loyal to the British, however, mental and physical breakdowns were common, and a particular type of hypochondriasis (" protection fever ") was described. After the peace of 1783, unwonted freedom led to a further form of insanity called by him anarchia ". Although French writers had noted mental accompaniments to their revolution, it seemed that Rush (though not entirely unbiased) could be credited with one of the earliest attempts to establish a causal correlation between social upheaval and mental "
consequence.
This concept,
Professor Rosen explained, spread century, and Rudolf Virchow in 1848 put forward a theory of " epidemic psychoses " indicative, he said, of major disturbances in man’s life; and he distinguished between " artificial " (i.e., social) and " natural " phenomena. In the following year he carried the idea further, suggesting that mental and physical epidemics came and went at the turning-points of civilisation and could give us insight into the popular as
widely during the
next
1.
Lancet, 1958, i, 419.
feelings of the time; but Griesinger regarded political change as an aggravating factor rather than a cause. At about the middle of the 19th century the concept of the " rising tide of madness " came to the fore, and it was slightly comforting to realise that the pessimists of today were the descendants of such a long line of Jeremiahs. On the positive side, a consequence of these views was an attack on the social structure itself with the aim of lessening the stresses therein: Hawkes in 1857 argued for wide and enlightened social reforms. Towards the end of the century a number of workers tried to provide a better factual basis by studying the incidence of insanity in different places and at different times; much evidence was in conflict, but the work of Durkheim on suicide was outstanding. Unfortunately the great discoveries in pathology and bacteriology overshadowed this work, although interest in it was now active. Regarding future work, Professor Rosen concluded that certain social variables, such as wars, epidemics, or slumps, should be defined and studied at sociological, psychiatric, and physiological levels, and along the time axis. He hoped that the historian, by clarifying issues in terms of their backgrounds and showing linkages not readily apparent, could make some contribution to the multidisciplinary approach. Few would disagree with him. CONGENITAL MALFORMATIONS
IT has been apparent for many years that the best way study associations between events in the early months of pregnancy and congenital malformations is prospectively. To go back into the pregnancy history after the birth of the malformed child is, in general, unsatisfactory,
to
unless the investigation is carefully controlled. This method led to an overestimate of the risk to the foetus after rubella; Hill et al.l now estimate from prospective studies that the risk of major defect is 50% in the first month, 25% in the second, and 17% in the third. They suggest, however, that the risk may vary from year to year and between one counrry and another. With careful controls, Stewart et al. have used the retrospective method more successfully in relation to malignant disease in childhood. Hill, A. B., Doll, R., Galloway, T. McL., Hodges, J. P. W. Brit. J. prev. soc. Med. 1958, 12, 1. 2. Stewart, A., Webb, J., Hewitt, D. Brit. med. J. 1958, i, 1495. 1.
135 CHRONIC IDIOPATHIC JAUNDICE
One method of conducting a prospective inquiry is to use the records of maternity hospitals, listing the incidents recorded in pregnancy and then noting the result of the pregnancy. Carter3 reported a study of this kind on about 15,000 deliveries in a London maternity hospital and found that none of the commonly recorded events in pregnancy were followed by a significant increase in the rate of malformation. There was a suggestion, however, that the rate might be higher after threatened abortion; and Turnbull and Walkerhave since also found, though again not at a high level of significance, a greater rate after threatened abortions. Hospital records, while satisfactory for such items as mother’s age and parity, inevitably give incomplete information about events early in pregnancy. The ideal is for a single trained observer to make special inquiry of the mother about the third month in pregnancy, and for this observer then to await the result of the pregnancy. The first general prospective study of this kind has now been reported by Dr. Alison McDonald.5
IN 1954,1 under the title a New Liver Disease, we drew attention to an apparently rare disorder of the liver reported independently by Dubin and Johnson2 and Sprinz and Nelson.3 In the past four years an additional 36 cases have been reported, bringing the total to 50from which it may be inferred that the condition is by no means as rare as was at first thought by its discoverers. A summary of these 50 cases by Dubin 4 should prove a valuable basis for further work. Dubin suggests that the fundamental defect is a genetically determined impairment of the excretory functions of the liver, which reveals itself clinically in intermittent attacks of jaundice with biliuria and sometimes pale stools. The onset may be insidious or acute, resembling an attack of infective hepatitis, or may follow some other disease or stress such as pneumonia, pregnancy, or immunisation. The attacks are usually associated with malaise, pain irt the right hypochondrium, nausea, and vomiting and diarrhoea. Between the attacks the jaundice almost disappears, although in most cases the serum-bilirubin remains more or less increased. Laboratory investigations indicate an obstructive type of jaundice, since some 60% of the serum-bilirubin is of the direct-reacting variety and bile is present in the urine; and, although the serumalkaline-phosphatase is rarely increased, there is little evidence of parenchymal damage and the serum-proteins are within normal limits. It is, therefore, hardly surprising that in 31 of these 50 patients laparotomy was undertaken for the relief of biliary obstruction; this was not found in a single case, although gallstones were present in 5. Of these first 50 patients only 9 were women; but, since the American Armed Forces Institute of Pathology was the chief case-finding source, the sex-distribution is obviously biased. The world-wide distribution of sporadic cases suggests that all ethnic groups are
McDonald interviewed 3295 mothers at the time of in the fourth or fifth month of pregnancy-at the Watford and St. Albans clinics in 1952-55. She was able to discover the outcome of 3216 of these pregnancies. There were 72 miscarriages and 63 stillbirths. Nearly all the surviving infants were examined by doctors and the majority by a paediatrician. Necropsies were performed on all but 8 of the stillborn and all but 4 of the 35 infants who died neonatally.
booking-this was mostly
Major malformations were found in 50 (1’5%) and minor malformations in 72 (2-3%). These rates agree well with those in other series of booked cases (hospital series including emergency admissions naturally show a higher rate) in which the children are not followed beyond the neonatal period. For the minor malformations there was no association with any event early in pregnancy. This was true, too, for the major malformations and threatened abortions, extramarital conception, injury, fainting, uterine retroversion, rhesus incompatibility, marked anxiety, and emotional shock. The mothers of the children with major malformations had an above-average incidence in early pregnancy of fairly heavy work, acute febrile illness, active or quiescent pulmonary tuberculosis, and anaemia. Inevitably the number of mothers affected in these ways was small and the associations do not reach high levels of significance. It is noteworthy that the 6 mothers who had a specific fever early in pregnancy (pertussis in 2, mumps in 2, rubella in 1, infectious hepatitis in 1) all had normal babies.
susceptible.
This survey shows how far we are from having any idea of the cause of most congenital malformations. It is known that relatively few are essentially genetically determined, though for many there is evidence of genetic predisposition. Environmental factors must be playing some part in the causation of most malformations, but none of the common events in pregnancy, and only rubella and toxoplasmosis among rare events, have been convincingly incriminated. There has been much more success in relating certain common malformations to social class, maternal age, birth-order, geography, and season of the year. These, however, afford only indirect clues, and the’ primary environmental factors concerned in most malformations remain unknown. ’
3. 4. 5.
Carter, C. O. J. Obstet. Gynœc., Brit. Emp. 1950, 57, 897. Turnbull, E. P., Walker, J. ibid. 1956, 63, 553. McDonald, A. D. New Engl. J. Med. 1958, 258, 767.
°
The morbid anatomy of the condition has been studied almost exclusively by biopsy, either by needle aspiration or laparotomy. The one outstanding abnormality is the remarkable colour of the liver-variously described as black, green, or mahogany-owing to accumulation in the centrilobular cells of large amounts of coarse yellow-brown pigment granules. These give histochemical reactions that identify them most closely with the lipofuscins, from which they differ mainly by their coarseness and persistence. Other hepatic abnormalities such as necrosis or fatty infiltration are rare and may be regarded as mainly incidental. Repeated biopsies with intervals of up to four years have shown no evidence of progressive hepatic injury; and this is confirmed by the complete lack of correlation between the duration of the disease and the intensity of the hepatic abnormality, as well as by the excellent prognosis as regards life expectancy. The nature of the underlying dysfunction is still not precisely known. Since the greater part of the serumbilirubin is of the direct-reacting variety the fault cannot be in the mechanism that converts bilirubin to its glucuronide, but is presumably in the mechanism of excretion that follows this conjugation. Other evidence of impaired excretion is obtained with bromsulphalein, and from attempts to display the gallbladder by oral cholecysto1. 2. 3. 4.
Lancet, 1954, ii, 1111. Dubin, I. N., Johnson, F.B. Medicine, 1954, 33, 155. Sprinz, H., Nelson, R. S. Ann. intern. Med. 1954, 41, 952. Dubin, I. N. Amer. J. Med. 1958, 24, 268.
make the crew understand that salt deficiency is something which anyone but a fool will take trouble to avoid. But ships with fewer than 100 people on board do not have to carry a doctor. Dr. LEITHEAD and his colleagues suggest various ways Young men are casual, and a certain foolhardiness befits seafarers. But these are poor consolations after in which the risks of these voyages could be reduced. a man has died because he did not bother to take extra But there is another that leaps to the eye. Granted that salt at meals, or thought the suggestion soft. Surely, one cannot expect to have a fully qualified medical man people who make use of scientific discoveries, and live in every vessel at sea, why should there be this immense the new kind of lives that science has made possible, difference between the medical care of 101 men, who bught to be willing to listen also to what science says must have a registered medical practitioner, and of 99 about the preservation of their health-and safety in the who need have nobody trained to advise them or attend new artificial environments ? But the necessary knowwisely to those minor illnesses which in the tropics are ledge needs to be supplied to them repeatedly and with so uncomfortably liable to become major ? Many years conviction; and, though many senior officers are inter- have now passed since the Association of Sea and Air ested, they mostly lack time for promoting preventive Port Health Authorities recommended that the smaller medicine in detail. Of course, if the ship has a doctor, ships should each carry a sickbay steward. We must he will be able to overcome irrelevant prejudices and ask why this is not yet done.
On each voyage, acclimatisation must be achieved almost afresh, and there is a danger period, of a week or more, until the body has learnt to conserve salt by reducing the salt content of the sweat.
Annotations
ORIGINS
OF SOCIAL PSYCHIATRY
IT is commonly believed that a real increase in mental breakdown is following on the raised tempo of modem life and our rapid cultural changes. Unfortunately the statistics are still so fallible, and the boundaries of mental health and illness so hazy, that fact can scarcely be distinguished from fallacy-let alone from fantasy. Some aspects of the " horizontal " approach, as it were, to culture and mental illness by G. M. Carstairs in his anthropological work were lately reviewed in these columns ’-; and on July 8 at the Institute of Psychiatry, London, Prof. George Rosen, of Columbia University, " a vertical" or longitudinal view. presented
In a scholarly address he pointed out that the concept of sociocultural determination in mental illness is not by any means new. Benjamin Rush studied the effects of the American Revolution on the participants: being an ardent revolutionary himself, he noticed among his ranks an increase in health and happiness, the cure of hysterical disorders among the women, and blessings granted to previously infertile marriages. Among those still loyal to the British, however, mental and physical breakdowns were common, and a particular type of hypochondriasis (" protection fever ") was described. After the peace of 1783, unwonted freedom led to a further form of insanity called by him anarchia ". Although French writers had noted mental accompaniments to their revolution, it seemed that Rush (though not entirely unbiased) could be credited with one of the earliest attempts to establish a causal correlation between social upheaval and mental "
consequence.
This concept,
Professor Rosen explained, spread century, and Rudolf Virchow in 1848 put forward a theory of " epidemic psychoses " indicative, he said, of major disturbances in man’s life; and he distinguished between " artificial " (i.e., social) and " natural " phenomena. In the following year he carried the idea further, suggesting that mental and physical epidemics came and went at the turning-points of civilisation and could give us insight into the popular as
widely during the
next
1.
Lancet, 1958, i, 419.
feelings of the time; but Griesinger regarded political change as an aggravating factor rather than a cause. At about the middle of the 19th century the concept of the " rising tide of madness " came to the fore, and it was slightly comforting to realise that the pessimists of today were the descendants of such a long line of Jeremiahs. On the positive side, a consequence of these views was an attack on the social structure itself with the aim of lessening the stresses therein: Hawkes in 1857 argued for wide and enlightened social reforms. Towards the end of the century a number of workers tried to provide a better factual basis by studying the incidence of insanity in different places and at different times; much evidence was in conflict, but the work of Durkheim on suicide was outstanding. Unfortunately the great discoveries in pathology and bacteriology overshadowed this work, although interest in it was now active. Regarding future work, Professor Rosen concluded that certain social variables, such as wars, epidemics, or slumps, should be defined and studied at sociological, psychiatric, and physiological levels, and along the time axis. He hoped that the historian, by clarifying issues in terms of their backgrounds and showing linkages not readily apparent, could make some contribution to the multidisciplinary approach. Few would disagree with him. CONGENITAL MALFORMATIONS
IT has been apparent for many years that the best way study associations between events in the early months of pregnancy and congenital malformations is prospectively. To go back into the pregnancy history after the birth of the malformed child is, in general, unsatisfactory,
to
unless the investigation is carefully controlled. This method led to an overestimate of the risk to the foetus after rubella; Hill et al.l now estimate from prospective studies that the risk of major defect is 50% in the first month, 25% in the second, and 17% in the third. They suggest, however, that the risk may vary from year to year and between one counrry and another. With careful controls, Stewart et al. have used the retrospective method more successfully in relation to malignant disease in childhood. Hill, A. B., Doll, R., Galloway, T. McL., Hodges, J. P. W. Brit. J. prev. soc. Med. 1958, 12, 1. 2. Stewart, A., Webb, J., Hewitt, D. Brit. med. J. 1958, i, 1495. 1.
135 CHRONIC IDIOPATHIC JAUNDICE
One method of conducting a prospective inquiry is to use the records of maternity hospitals, listing the incidents recorded in pregnancy and then noting the result of the pregnancy. Carter3 reported a study of this kind on about 15,000 deliveries in a London maternity hospital and found that none of the commonly recorded events in pregnancy were followed by a significant increase in the rate of malformation. There was a suggestion, however, that the rate might be higher after threatened abortion; and Turnbull and Walkerhave since also found, though again not at a high level of significance, a greater rate after threatened abortions. Hospital records, while satisfactory for such items as mother’s age and parity, inevitably give incomplete information about events early in pregnancy. The ideal is for a single trained observer to make special inquiry of the mother about the third month in pregnancy, and for this observer then to await the result of the pregnancy. The first general prospective study of this kind has now been reported by Dr. Alison McDonald.5
IN 1954,1 under the title a New Liver Disease, we drew attention to an apparently rare disorder of the liver reported independently by Dubin and Johnson2 and Sprinz and Nelson.3 In the past four years an additional 36 cases have been reported, bringing the total to 50from which it may be inferred that the condition is by no means as rare as was at first thought by its discoverers. A summary of these 50 cases by Dubin 4 should prove a valuable basis for further work. Dubin suggests that the fundamental defect is a genetically determined impairment of the excretory functions of the liver, which reveals itself clinically in intermittent attacks of jaundice with biliuria and sometimes pale stools. The onset may be insidious or acute, resembling an attack of infective hepatitis, or may follow some other disease or stress such as pneumonia, pregnancy, or immunisation. The attacks are usually associated with malaise, pain irt the right hypochondrium, nausea, and vomiting and diarrhoea. Between the attacks the jaundice almost disappears, although in most cases the serum-bilirubin remains more or less increased. Laboratory investigations indicate an obstructive type of jaundice, since some 60% of the serum-bilirubin is of the direct-reacting variety and bile is present in the urine; and, although the serumalkaline-phosphatase is rarely increased, there is little evidence of parenchymal damage and the serum-proteins are within normal limits. It is, therefore, hardly surprising that in 31 of these 50 patients laparotomy was undertaken for the relief of biliary obstruction; this was not found in a single case, although gallstones were present in 5. Of these first 50 patients only 9 were women; but, since the American Armed Forces Institute of Pathology was the chief case-finding source, the sex-distribution is obviously biased. The world-wide distribution of sporadic cases suggests that all ethnic groups are
McDonald interviewed 3295 mothers at the time of in the fourth or fifth month of pregnancy-at the Watford and St. Albans clinics in 1952-55. She was able to discover the outcome of 3216 of these pregnancies. There were 72 miscarriages and 63 stillbirths. Nearly all the surviving infants were examined by doctors and the majority by a paediatrician. Necropsies were performed on all but 8 of the stillborn and all but 4 of the 35 infants who died neonatally.
booking-this was mostly
Major malformations were found in 50 (1’5%) and minor malformations in 72 (2-3%). These rates agree well with those in other series of booked cases (hospital series including emergency admissions naturally show a higher rate) in which the children are not followed beyond the neonatal period. For the minor malformations there was no association with any event early in pregnancy. This was true, too, for the major malformations and threatened abortions, extramarital conception, injury, fainting, uterine retroversion, rhesus incompatibility, marked anxiety, and emotional shock. The mothers of the children with major malformations had an above-average incidence in early pregnancy of fairly heavy work, acute febrile illness, active or quiescent pulmonary tuberculosis, and anaemia. Inevitably the number of mothers affected in these ways was small and the associations do not reach high levels of significance. It is noteworthy that the 6 mothers who had a specific fever early in pregnancy (pertussis in 2, mumps in 2, rubella in 1, infectious hepatitis in 1) all had normal babies.
susceptible.
This survey shows how far we are from having any idea of the cause of most congenital malformations. It is known that relatively few are essentially genetically determined, though for many there is evidence of genetic predisposition. Environmental factors must be playing some part in the causation of most malformations, but none of the common events in pregnancy, and only rubella and toxoplasmosis among rare events, have been convincingly incriminated. There has been much more success in relating certain common malformations to social class, maternal age, birth-order, geography, and season of the year. These, however, afford only indirect clues, and the’ primary environmental factors concerned in most malformations remain unknown. ’
3. 4. 5.
Carter, C. O. J. Obstet. Gynœc., Brit. Emp. 1950, 57, 897. Turnbull, E. P., Walker, J. ibid. 1956, 63, 553. McDonald, A. D. New Engl. J. Med. 1958, 258, 767.
°
The morbid anatomy of the condition has been studied almost exclusively by biopsy, either by needle aspiration or laparotomy. The one outstanding abnormality is the remarkable colour of the liver-variously described as black, green, or mahogany-owing to accumulation in the centrilobular cells of large amounts of coarse yellow-brown pigment granules. These give histochemical reactions that identify them most closely with the lipofuscins, from which they differ mainly by their coarseness and persistence. Other hepatic abnormalities such as necrosis or fatty infiltration are rare and may be regarded as mainly incidental. Repeated biopsies with intervals of up to four years have shown no evidence of progressive hepatic injury; and this is confirmed by the complete lack of correlation between the duration of the disease and the intensity of the hepatic abnormality, as well as by the excellent prognosis as regards life expectancy. The nature of the underlying dysfunction is still not precisely known. Since the greater part of the serumbilirubin is of the direct-reacting variety the fault cannot be in the mechanism that converts bilirubin to its glucuronide, but is presumably in the mechanism of excretion that follows this conjugation. Other evidence of impaired excretion is obtained with bromsulphalein, and from attempts to display the gallbladder by oral cholecysto1. 2. 3. 4.
Lancet, 1954, ii, 1111. Dubin, I. N., Johnson, F.B. Medicine, 1954, 33, 155. Sprinz, H., Nelson, R. S. Ann. intern. Med. 1954, 41, 952. Dubin, I. N. Amer. J. Med. 1958, 24, 268.