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CONGENITAL MALFORMATIONS AND ORAL POLIOVIRUS VACCINATION DURING PREGNANCY
771 no longer on the scene when the disease protagonists were 1
died in 1833. In that year, the East India Company and went to O’Shaughnessy joined India. There he interested himself, not with cholera, but with chemistry, electricity, and telegraphy. He was knighted in 1856, not for work in medicine, but for establishing a telegraph service between the main centres of India which was said to have influenced the result of the Indian mutiny.1 William O’Shaughnessy’s third claim to fame was that, on returning from India, he introduced cannabis to England and Europe as a potent medication and analgesic for the treatment of tetanus, rheumatism, and epilepsy.2 He died in 1889, but obituary notices make no mention of his pioneering research1-his analyses of the blood and excreta of cholera patients, his deduction of the mechanism of the changes in composition, and his proposal
struck again.
Latta
Preventive Medicine CONGENITAL MALFORMATIONS AND ORAL POLIOVIRUS VACCINATION DURING PREGNANCY TIINA HARJULEHTO1 TAPANI HOVI3
TIMO ARO2 LAURI SAXÉN1
Departments of Pathology1 and Public Health,2 University of Helsinki, and National Public Health Institute,3 Helsinki, Finland
February, 1985, mass vaccination with poliovirus vaccine (OPV) was started during a poliomyelitis outbreak in Finland. Pregnant women were advised to take the vaccination. Judged as the rate of reported malformations, OPV during early pregnancy had no harmful effects on fetal development. Summary
In
live oral
INTRODUCTION
MATERNAL virus infection during early pregnancy can be transplacentally transmitted and cause fetal damage,l and there have been several case reports of maternal poliomyelitis associated with fetal infection and impaired
of rational treatment, which was put into practice by Thomas Latta and Robert Lewins of Leith. All this when O’Shaughnessy was 22 and 23 years old, and when chemical pathology was an embryonic science. Dr Lewins, in reporting Latta’s second case, wrote to The Lancet on May 18, 1832: "Verily, Sir, this is an astonishing method of medication, and I predict will lead to wonderful changes and improvements in the practice of medicine". He was right. Yet the names of O’Shaughnessy, Latta, and Lewins cannot be found in any major work on general medical history. REFERENCES
Heyningen WE, Seal JR. Cholera: the American scientific experience 1947-1980. Boulder, Colorado: Westview Press, 1983: 1-25. 2. Nahas GG. Marihuana—deceptive weed. New York: Raven Press, 1973: 7. 1.
van
All other quotations are from The Lancet 1830-31, vol ii; 1831-32, vols i and ii; 1832-33 vol i.
development.2-4 However, information on fetal development following maternal vaccination with live poliovirus is scanty. Some studies indicate that oral poliovirus vaccination (OPV) during pregnancy may damage the embryo, and the authors have advised against vaccination of pregnant women.5-7 Other workers have considered OPV vaccination to be safe during pregnancy.8,9 The populations studied have been small, with 31 to 310 vaccinated mothers, and the risks of OPV during pregnancy remain unclear. Nevertheless, OPV is widely used in mass vaccination programmes, which may include pregnant mothers and women of childbearing age-because a decision not to vaccinate pregnant women would require exclusion of all women of childbearing age, who would be difficult to protect against secondary infection, which would make a population-wide vaccination campaign impossible. An outbreak of 10 cases of poliomyelitis occurred in Finland between August, 1984, and January, 1985, associated with widespread circulation of the wild type 3 poliovirus. to An extensive, nationwide vaccination campaign was organised: a dose of trivalent OPV was recommended to the entire adult population except people with known or suspected immunodeficiency. OPV had in regular childhood never been used in Finland immunisations. Between February 10, and March 15, 1985,
Monthly prevalence of all congenital malformations in Finland,
1982-1986.
Closed circles indicate postvaccination period (Finnish Register of Congenital
Malformations).
772 EXPECTED AND OBSERVED
(REPORTED) NUMBER OF ALL
MALFORMATIONS, CNS DEFECTS, AND OROFACIAL CLEFTS
Correspondence should be addressed to L. S., Department of Pathology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland.
REFERENCES
*Expected (E) numbers for 1985 were calculated from the prevalence figures corresponding months in 1982 to 1984 based on 97 244 and 48 341 deliveries, respectively, and shown as mean (SD). 0 = observed. of
the nationwide vaccination coverage for adults was 94%.10 The short duration of the vaccination campaign and the high vaccination rate provided the opportunity for an epidemiological study on the possible association of OPV and impaired fetal development. MATERIALS AND METHODS
All children with reported congenital malformations who were bom in 1982 to 1986 were included in the study. In Finland, notification of all malformations detected in children during their first year of life has been compulsory since 1963. These data, completed with information from death certificates, are available at the Register of Congenital Malformations.’1 The overall incidence of reported malformations is about 2% of approximately 60 000 births annually, in a population of 49 million. The monthly prevalence was calculated for all malformations from 1982 to 1986, including the post-vaccination period. Furthermore, the prevalence of two "indicator" defects was calculated because figures for the total prevalence of reported malformations include a wide variety of conditions that may not be caused by impaired organogenesis. The two indicator groups, analysed separately, were defects of the central nervous system (CNS) and orofacial clefts, chosen because of their high detection and reporting rates.12 The expected number of indicator defects for 1985 was calculated from the prevalence figures for the corresponding months for 1982 to 1984, and compared with the numbers observed after vaccination in 1985. Malformations due to disturbed organogenesis should be induced during the first trimester of pregnancy: children at this stage of development who were exposed to OPV in February-March, 1985, were expected to be born between August 12 and December 7 of that year. To include premature births, not uncommon among defective children, and because the virus may have caused viraemia during the two weeks after completion of the vaccination programme, the broadest study group consisted of all children born in July to December, 1985 (period I). The group of children exposed to OPV at 2-8 weeks gestation were expected to be born in September to November, 1985 (period II). RESULTS AND DISCUSSION
No significant deviations from the baseline prevalence for all malformations were observed during the months after vaccination (see figure). The table shows that the observed numbers of malformations for either indicator defect during either study period did not increase significantly. We therefore suggest that OPV had no harmful effects on fetal development, monitored as overall prevalence of malformations or as two specific indicator defects. However, the results do not exclude an effect measurable by other criteria of fetal development, and an extensive analysis of approximately 5000 children exposed to OPV during early development will pay special attention to possible increases in rare types of congenital defects that have escaped this
analysis.
1. Kurent JE, Sever JL. Infectious diseases. In: Wilson JG, Fraser FC, eds. Handbook of teratology, vol 1. New York: Plenum Press, 1967: 225-59. 2. Aycock WL, Ingalls TH. Maternal disease as a principle in the epidemiology of congenital anomalies. AmJ Med Sci 1946; 212: 366-79. 3. Grönvall H, Selander P. Some virus diseases during pregnancy, their effect on fetus. Nord Med 1948; 37: 409-15. 4. Hardy JB. Fetal consequences of maternal viral infections in pregnancy. Arch Otolaryngol 1973; 98: 218-27. 5. Kleinebrecht J. Virus-infektion und Impfung in der Schwangerschaft. Dtsch Ärtzbl 1974; 17: 1239-40. 6. Burton AE, Robinson ET, Harper WF, et al. Fetal damage after accidental polio vaccination of an immune mother. J R Coll Gen Pract 1984; 34: 390-94. 7. Just VM, Burgin-Wolff A. Der Einfluss der oralen Poliomyelitisimpfung auf die Schwangerschaft. Schweiz Med Wochenschr 1963; 93: 1551-56. 8. Prem KA, Fergus JW, Mathers JE, et al. Vaccination of pregnant women and young infants with trivalent oral attenuated live poliomyelitis vaccine. Pan Am Hlth Org Sci Publ 1960; 50: 207-27. 9. Stickl H. Kann die Schluckimpfung gegen Kinderlähmung bei Schwangeren zu intrauterinen Fruchtschäden führen? Munch Med Wochenschr 1965; 107: 2337-42. 10. Hovi T, Cantell K, Huovilainen A, et al. Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population. Lancet 1986; i: 1427-32. 11. Saxén L, Klemetti A, Haro SA. A matched-pair register for studies of selected congenital defects. Am J Epidemiol 1974; 100: 297-306. 12. Saxén L. Twenty years of study of the etiology of congenital malformations in Finland. In: Kalter H, ed. Issues and reviews in teratology, vol 2. New York: Plenum Press, 1983: 73-110.
Point of View RESOURCE ALLOCATION AND BIOETHICS
J. M. DUGGAN Gastroenterology Department, Royal Newcastle Hospital, PO Box 664J, Newcastle, New South Wales 2300, Australia PROFICIENCY in bioethics and economic analysis are not widely regarded as part of the intellectual baggage of the medical technocrat, nor indeed of the practising clinician. However, the widening gulf between the costs of medical technology and the capacity of economic systems to pay for them have led to reappraisal of medical care provision and its justification, even in affluent western societies. In the US, for example, despite the allocation of about 115% of the gross national product to health care, an estimated 38 million people have no medical insurance for routine care or for catastrophic illness. In many other countries, whatever the source of funds, there is a growing gap between the ability and willingness of governments or insurers to pay and the demands of medical consumers or providers. The tensions produced will be familiar to most medical practitionersantagonism and friction occur between branches and disciplines which are fighting for a larger share of limited resources: geriatrics versus oncology, AIDS versus neonatal intensive care, preventive medicine versus molecular biology, and so on. Hiatt1 described this several years ago as "protecting the medical commons", where medicine is compared to a village green upon which the villagers allow their cattle to graze in proportion to the forage available. Should a villager put an extra cow on the common, correctly reasoning that just one more would not damage the pasture, and should all the other villagers follow this example, then the pasture would be destroyed and the herd would die.
died in 1833. In that year, the East India Company and went to O’Shaughnessy joined India. There he interested himself, not with cholera, but with chemistry, electricity, and telegraphy. He was knighted in 1856, not for work in medicine, but for establishing a telegraph service between the main centres of India which was said to have influenced the result of the Indian mutiny.1 William O’Shaughnessy’s third claim to fame was that, on returning from India, he introduced cannabis to England and Europe as a potent medication and analgesic for the treatment of tetanus, rheumatism, and epilepsy.2 He died in 1889, but obituary notices make no mention of his pioneering research1-his analyses of the blood and excreta of cholera patients, his deduction of the mechanism of the changes in composition, and his proposal
struck again.
Latta
Preventive Medicine CONGENITAL MALFORMATIONS AND ORAL POLIOVIRUS VACCINATION DURING PREGNANCY TIINA HARJULEHTO1 TAPANI HOVI3
TIMO ARO2 LAURI SAXÉN1
Departments of Pathology1 and Public Health,2 University of Helsinki, and National Public Health Institute,3 Helsinki, Finland
February, 1985, mass vaccination with poliovirus vaccine (OPV) was started during a poliomyelitis outbreak in Finland. Pregnant women were advised to take the vaccination. Judged as the rate of reported malformations, OPV during early pregnancy had no harmful effects on fetal development. Summary
In
live oral
INTRODUCTION
MATERNAL virus infection during early pregnancy can be transplacentally transmitted and cause fetal damage,l and there have been several case reports of maternal poliomyelitis associated with fetal infection and impaired
of rational treatment, which was put into practice by Thomas Latta and Robert Lewins of Leith. All this when O’Shaughnessy was 22 and 23 years old, and when chemical pathology was an embryonic science. Dr Lewins, in reporting Latta’s second case, wrote to The Lancet on May 18, 1832: "Verily, Sir, this is an astonishing method of medication, and I predict will lead to wonderful changes and improvements in the practice of medicine". He was right. Yet the names of O’Shaughnessy, Latta, and Lewins cannot be found in any major work on general medical history. REFERENCES
Heyningen WE, Seal JR. Cholera: the American scientific experience 1947-1980. Boulder, Colorado: Westview Press, 1983: 1-25. 2. Nahas GG. Marihuana—deceptive weed. New York: Raven Press, 1973: 7. 1.
van
All other quotations are from The Lancet 1830-31, vol ii; 1831-32, vols i and ii; 1832-33 vol i.
development.2-4 However, information on fetal development following maternal vaccination with live poliovirus is scanty. Some studies indicate that oral poliovirus vaccination (OPV) during pregnancy may damage the embryo, and the authors have advised against vaccination of pregnant women.5-7 Other workers have considered OPV vaccination to be safe during pregnancy.8,9 The populations studied have been small, with 31 to 310 vaccinated mothers, and the risks of OPV during pregnancy remain unclear. Nevertheless, OPV is widely used in mass vaccination programmes, which may include pregnant mothers and women of childbearing age-because a decision not to vaccinate pregnant women would require exclusion of all women of childbearing age, who would be difficult to protect against secondary infection, which would make a population-wide vaccination campaign impossible. An outbreak of 10 cases of poliomyelitis occurred in Finland between August, 1984, and January, 1985, associated with widespread circulation of the wild type 3 poliovirus. to An extensive, nationwide vaccination campaign was organised: a dose of trivalent OPV was recommended to the entire adult population except people with known or suspected immunodeficiency. OPV had in regular childhood never been used in Finland immunisations. Between February 10, and March 15, 1985,
Monthly prevalence of all congenital malformations in Finland,
1982-1986.
Closed circles indicate postvaccination period (Finnish Register of Congenital
Malformations).
772 EXPECTED AND OBSERVED
(REPORTED) NUMBER OF ALL
MALFORMATIONS, CNS DEFECTS, AND OROFACIAL CLEFTS
Correspondence should be addressed to L. S., Department of Pathology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland.
REFERENCES
*Expected (E) numbers for 1985 were calculated from the prevalence figures corresponding months in 1982 to 1984 based on 97 244 and 48 341 deliveries, respectively, and shown as mean (SD). 0 = observed. of
the nationwide vaccination coverage for adults was 94%.10 The short duration of the vaccination campaign and the high vaccination rate provided the opportunity for an epidemiological study on the possible association of OPV and impaired fetal development. MATERIALS AND METHODS
All children with reported congenital malformations who were bom in 1982 to 1986 were included in the study. In Finland, notification of all malformations detected in children during their first year of life has been compulsory since 1963. These data, completed with information from death certificates, are available at the Register of Congenital Malformations.’1 The overall incidence of reported malformations is about 2% of approximately 60 000 births annually, in a population of 49 million. The monthly prevalence was calculated for all malformations from 1982 to 1986, including the post-vaccination period. Furthermore, the prevalence of two "indicator" defects was calculated because figures for the total prevalence of reported malformations include a wide variety of conditions that may not be caused by impaired organogenesis. The two indicator groups, analysed separately, were defects of the central nervous system (CNS) and orofacial clefts, chosen because of their high detection and reporting rates.12 The expected number of indicator defects for 1985 was calculated from the prevalence figures for the corresponding months for 1982 to 1984, and compared with the numbers observed after vaccination in 1985. Malformations due to disturbed organogenesis should be induced during the first trimester of pregnancy: children at this stage of development who were exposed to OPV in February-March, 1985, were expected to be born between August 12 and December 7 of that year. To include premature births, not uncommon among defective children, and because the virus may have caused viraemia during the two weeks after completion of the vaccination programme, the broadest study group consisted of all children born in July to December, 1985 (period I). The group of children exposed to OPV at 2-8 weeks gestation were expected to be born in September to November, 1985 (period II). RESULTS AND DISCUSSION
No significant deviations from the baseline prevalence for all malformations were observed during the months after vaccination (see figure). The table shows that the observed numbers of malformations for either indicator defect during either study period did not increase significantly. We therefore suggest that OPV had no harmful effects on fetal development, monitored as overall prevalence of malformations or as two specific indicator defects. However, the results do not exclude an effect measurable by other criteria of fetal development, and an extensive analysis of approximately 5000 children exposed to OPV during early development will pay special attention to possible increases in rare types of congenital defects that have escaped this
analysis.
1. Kurent JE, Sever JL. Infectious diseases. In: Wilson JG, Fraser FC, eds. Handbook of teratology, vol 1. New York: Plenum Press, 1967: 225-59. 2. Aycock WL, Ingalls TH. Maternal disease as a principle in the epidemiology of congenital anomalies. AmJ Med Sci 1946; 212: 366-79. 3. Grönvall H, Selander P. Some virus diseases during pregnancy, their effect on fetus. Nord Med 1948; 37: 409-15. 4. Hardy JB. Fetal consequences of maternal viral infections in pregnancy. Arch Otolaryngol 1973; 98: 218-27. 5. Kleinebrecht J. Virus-infektion und Impfung in der Schwangerschaft. Dtsch Ärtzbl 1974; 17: 1239-40. 6. Burton AE, Robinson ET, Harper WF, et al. Fetal damage after accidental polio vaccination of an immune mother. J R Coll Gen Pract 1984; 34: 390-94. 7. Just VM, Burgin-Wolff A. Der Einfluss der oralen Poliomyelitisimpfung auf die Schwangerschaft. Schweiz Med Wochenschr 1963; 93: 1551-56. 8. Prem KA, Fergus JW, Mathers JE, et al. Vaccination of pregnant women and young infants with trivalent oral attenuated live poliomyelitis vaccine. Pan Am Hlth Org Sci Publ 1960; 50: 207-27. 9. Stickl H. Kann die Schluckimpfung gegen Kinderlähmung bei Schwangeren zu intrauterinen Fruchtschäden führen? Munch Med Wochenschr 1965; 107: 2337-42. 10. Hovi T, Cantell K, Huovilainen A, et al. Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population. Lancet 1986; i: 1427-32. 11. Saxén L, Klemetti A, Haro SA. A matched-pair register for studies of selected congenital defects. Am J Epidemiol 1974; 100: 297-306. 12. Saxén L. Twenty years of study of the etiology of congenital malformations in Finland. In: Kalter H, ed. Issues and reviews in teratology, vol 2. New York: Plenum Press, 1983: 73-110.
Point of View RESOURCE ALLOCATION AND BIOETHICS
J. M. DUGGAN Gastroenterology Department, Royal Newcastle Hospital, PO Box 664J, Newcastle, New South Wales 2300, Australia PROFICIENCY in bioethics and economic analysis are not widely regarded as part of the intellectual baggage of the medical technocrat, nor indeed of the practising clinician. However, the widening gulf between the costs of medical technology and the capacity of economic systems to pay for them have led to reappraisal of medical care provision and its justification, even in affluent western societies. In the US, for example, despite the allocation of about 115% of the gross national product to health care, an estimated 38 million people have no medical insurance for routine care or for catastrophic illness. In many other countries, whatever the source of funds, there is a growing gap between the ability and willingness of governments or insurers to pay and the demands of medical consumers or providers. The tensions produced will be familiar to most medical practitionersantagonism and friction occur between branches and disciplines which are fighting for a larger share of limited resources: geriatrics versus oncology, AIDS versus neonatal intensive care, preventive medicine versus molecular biology, and so on. Hiatt1 described this several years ago as "protecting the medical commons", where medicine is compared to a village green upon which the villagers allow their cattle to graze in proportion to the forage available. Should a villager put an extra cow on the common, correctly reasoning that just one more would not damage the pasture, and should all the other villagers follow this example, then the pasture would be destroyed and the herd would die.