- Email: [email protected]
Epidemiologic aspects of hydatidiform mole in Israel
Epidemiologic aspects of hydatidiform
mole in
Israel MEIR
MATALON,
BARUCH Tel
M.D.*
MODAN,
Hashomer,
M.D.
I.rrael
A study based on all 534 newly diagnosed cases of hydatidiform mole in ]ewish women in Israel between 1950 and 1965 revealed a mean annual incidence of I :I,300 births. Incidence was relatively higher beyond the age of 40, independent of jarity. There were no interethnic differences except for a higher incidence in European-born women, 45 years of age and older. The risk of developing a second hydatidiform mole was about 20 times higher than for the first one. The incidence rose from I :2,400 births in 1950 to 1954 to 1:900 births in 1960 to 1965. This increase consisted of two components:(1) an increase in incidence in the 15 to 19 year age group, present in all ethnic categories, but limited to the more recent time period (1960 to 1965); (2) a marked increase in incidence in the 45+ age group from 1955 onward, primarily among European-born women.
1965 where no relation to socioeconomicstatus was observed, although some condition specific to the Far East might be responsible.g It is difficult to evaluate the meaning of variation in incidence observed for NM’s On the one hand, many patients with HM do not reach a hospital, many others are misdiagnosed,and the degree of recognition is correlated with the quality of medical care. On the other hand, in underdeveloped areas it is probable that a patient with HM has more chance to be hospitalized than one with a normal pregnancy, and, since data are based on hospital population, this will result in a high ratio to live births. In the present study, based on a nationwide record search, an attempt was made to assessto what extent the diseaseincidence differs among the main Israeli ethnic groups, which vary considerably in socioeconomic status but benefit from equally availabIe adequate medical care. A number of other
T H E M A R K E D variation in the incidence of hydatidiform mole (HM) between developed and underdeveloped countries1-9implies an environmental factor in the etiology of the disease. The highest frequencies have been described in the Far East, starting from 1: 125 births,3 and the lowest, 1:2,500, in Europe6 and the United States.7 The high frequency in Asia has been occasionally related to undernutrition, for instance, in the Philippines,l and in Hong Kong.3 This hypothesis was objected to by McCorriston*O on the basis of 94 HM casesin Hawaii between 1951 and From the Department of Clinical Efiidemiology, Tel Hashomer Government Hospital. The study wassupported by Research Agreement No. 06-125-2 from the United States Public Health Service. Received
for publication
April
21, 1971.
*This report is part of an M.D. thesis submitted by Dr. Matalon to the Hebrew University Medical School, Jerusalem, Israel. 107
108
Matalon
and
parameters of also studied. Materials
January Am. J. Obstet.
Modan
epidemiologic
and
interest
were
methods
The study was based on all cases of HM diagnosed in Israel between 1950 and 1965. Cases were ascertained through the medical record room listings of all general hospitals in Israel and gynecologic and/or obstetric specialty hospitals. Where no diagnostic listing was available in the hospital, a screening of the operating room records was made. Finally, a screening was made of the diagnostic listings in those departments of pathology where such a list was available. Arab women were excluded due to a lower rate of referral to hospitals. The criteria for inclusion of cases were based primarily on histologic diagnosis of HM by the individual pathologist in each hospital. Histologic confirmation was obtained in 99.2 per cent of the cases (95.2 per cent in the 1950 to 1954 time period and 99.8 per cent subsequently). The population figures were based on the 1961 census and subsequent estimates. Some of the computations were done with the aid of an IBM 360 computer. Results
Incidence. There
were 534 new cases of HM among Jewish women in Israel during this time period, including 12 women with recurrences. The mean annual incidence in the total period from 1950 to 1965 was 3.9 per 100,000 Jewish women or 7.9 per 100,000 women in the fertile age group (15 to 49). If the rate is computed on the basis of the number of live births, a rate of 0.75 per 1,000 live births or 1: 1,300 births is obtained. A more than twofold increase in incidence of HM was noted during the study period, from 0.41 per 1,000 live births (1: 2,400) in 1950 to 1954 to 0.69 (1: 1,500) in 1955 to 1959 and 1.06 (1:900) in 1960 to 1965 (Table I) . This increase is significant (p [p = 0] < 0.01). A similar trend of increase in incidence with time was also found in two hospitals in Boston.D The
1, 1972 Gynecol.
Table I. Mean annual incidence of hydatidiform mole among Jewish women in Israel ( 1950 to 1965) by chronologic time period Time
period
1950 - 1954 1955 - 1959 1960 - 1965
No.
of
87 150 297
cases
Rate/l,000 live births 0.41 0.69 1.06
marked increase in the observed incidence during the observed time periods could be related in part to a better awareness on the part of the population of the need to consult a gynecologist in the case of unexpected bleeding and of the physicians to look for a HM in each abortion case. However, a comparison of the incidence in the 3 time periods by age (Fig. 1) reveals that the increase with time is primarily due to two components : ( 1) an increase in the over 40 age groups in the 1955 to 1965 period, and (2) the appearance of an additional peak in the youngest age group ( 15 to 19) in 1960 to 1965. Of the two components, only the increase in older age which started in 1955 can be reasonably accounted for by better recognition. With regard to the 15 to 19 group, better recognition seems to be an insufficient explanation, because of its beonly after 1960. It is of lated appearance, interest that this recent appearance of a relatively increased incidence in the 15 to 19 age group, which is significantly different from the previous time period (p [Poisson] < 0.05), is consistent with the findings of Slocumb and Lund,‘l who indicated a similar trend in the disease incidence in younger age groups in the Rochester, New York, area. Since it seems that information regarding HM is incomplete for the earlier time period, further analysis will be limited to cases diagnosed during 1955 to 1965. Age. If age-specific incidence rates are computed on the basis of female population, peak incidence rates seem to occur in the 20 to 29 age group (Table II). But, if the rates are computed on the basis of births, incidence rates are about the same below the age of
Volume
112
Number
1
Epidemiologic
*("
54
to
IS
#
1s
aspects
40
of hydatidiform
45
mole
109
4 50
AEf
Fig. 1. Comparison of mean annual age-specific rates of hydatidiform women in Israel per 1,000 live births in 3 chronologic time periods. 40 with a subsequent increase, particularly beyond the age of 45. The rate for the 40 to 44 age group is significantly different (p [Poisson] < 0.05) from both the rates for the age groups above and below. This indicates that the peak in the 20 to 29 age group, observed in the rates based on the total fertile female population, is related to the higher fertility of this age group. Parity. Because of the obvious correlation between the woman’s age and the number of previous births, the factor of parity has to be examined separately. This is presented in Table III. It is evident that incidence rate
mole among Jewish
in each age group, including the increased rate beyond the age of 40, is independent of the number of previous deliveries, i.e., there are no significant differences in the rates ‘among parity groups. Consequently, parity does not seem to play a role in the disease etiology. Ethnic origin. If incidence rates are computed on the basis of the total female population in the fertile age, an apparently higher rate is present in all age groups among the Asian and African born as compared to the European born. However, because of the difference in fertility between the ethnic groups,
110
Matalon
and Modan Am.
i.e., a lower fertility rate among the European born, this comparison is invalid. Incidence rates by ethnic group based on the number of births do not reveal significant differences between the ethnic groups except for a markedly higher incidence in European-born women age 45 and over, as compared to the Asian-African and Israeli groups (p [ Poisson] < 0.05) (Table IV). The higher incidence in older European women is independent of parity since it is present in each parity group. Recurent mole. Eleven of the women had a recurrent mole during the study period. Of the 447 cases first diagnosed in the 1955 to 1965 period, for which better information is available, there were 9 recurrent cases. This yields a ratio of 1:50, i.e., about 20 times higher than the observed rate of 1: 1,100 live births for this period. The risk of a recurrent mole was smaller if normal deliveries had occurred in the intervening period. Thus, it is of interest that in 7 of the 9 women the second mole occurred within one year of the previous mole. In another woman the difference was 9 years but with a history of 4 abortions and no norma1 delivery. The patient was the only one who had a normal delivery in the two intervening years between the two moles. Comment The incidence of hydatidiform mole in Israeli Jewish women is in the same range as that in Western Europe and the United States.6-8 A similar incidence (1: I,1 15) was found in Los Angeles I2 for the 1950 to 1964 period, in BraziP (1: 1,071) in the 1951 to 1957 period, and in Australia14 (1: 962) for the years 1950 to 1966. In order to evaluate any trends correctly, incidence should be computed on the basis of live births and not on the basis of the female population. Otherwise, a more fertile group will present a higher incidence than a less fertile one, even when no difference in the risk of a woman to develop HM exists. For instance, it has been emphasized in some publications that the disease is most frequent in the third decade of Iife3-5r 7 and
January J. Obstet.
1, 1972 Gynecol.
Table II. Mean annual incidence of hydatidiform mole among Jewish women in Israel ( 1955 to 1965) per 100,000 women and per 1,000 live births, by age group Age &PUP 15-19 20-24 25-29 30-34 35-39 40-44 45+ Unknown
No. of Rate/lOO,OOO cases women+ 39 124 95 68 47 40 31 3
Totals
447
“In this only once.
computation
iDenominator
is women
Rate/l,000 live births
4.5 17.2 13.0 9.2 6.9 Et
1.1 0.8 0.6 0.7 1.0 3.2 11.3
8.9 recurrent age 45
0.9 cazes
were
considered
to 49.
that it is more prevalent among parous women.3y 5a 7 In our data, a peak in the 20 to 29 year age group and a parity effect could be observed which were solely associated with a larger number of births. When rates are computed per live births, a completely different age effect is noted; there are two peaks, a small one below the age of 20 and a marked one beyond the age of 40. Birth order in itself was not found to have any effect. Yen and MacMahonD could find no significant effect of parity either. The higher incidence in the 15 to 19 year age group in the more recent period from 1960 to 1965 is in line with the findings by Slocumb and Lundll on the basis of 18 cases diagnosed at Strong Memorial Hospital in Rochester, New York, and also noted in the study by Westerhout and associatesI from Los Angeles. Slocumb and Lund emphasize that the increase in the young age group is a recent phenomenon. They try to relate this increase to more frequent sexual intercourse in younger age groups in recent years. It does not seem plausible, however, that this would explain the higher incidence compared to the 20 to 34 year age group. Our findings are consistent with the notion that this is a relatively recent phenomenon; in 1950 to 1954 and 1955 to 1959 the incidence in the 15 to 19 year age group was similar to the following age groups up to the age
Volume Number
112 1
Epidemiologic
Table III. Mean annual incidence of hydatidiform Israel per 1,000 live births, by age group and parity
Age
group
< 20 20-24 25-29 30-34 35-39 40-44 45+ Unknown
No. 39 124 95 68 47 40 31 3
Totals
477
0
) Rate
No.
1.1 0.8 0.6 0.7 1.0 3.2 11.3
34 62 18 6 2 1 1
0.9
124
of previous
1
( Rate
No.
No.
( Rate
No.
1 Rate
4
0.0 0.7 0.4 0.8 1.5 3.0 33.3
5 16 16 7 7 8
0.0 0.4 0.5 0.8 0.8 3.3 ..i... ‘)‘,3
82
0.6
60
0.8
59
0.8
0.9
No. 3 13 18 22 25 12 1 94
Europe and America
Age
group
< 20 20-24 25-29 30-34 35-39 40-44 45+ Unknown Totals
No. 39 124 95 68 47 40 31 3 447
Rate
Rate
No.
1.1 0.8 0.6 0.7 1.0 3.2 11.2
7 18 15 13 16 :i
0.9
99
1.5 0.7 0.4 0.5 1.1 6;::
0.9
of 40, and only in 1960 to 1965 did a relatively increased incidence appear. On the other hand, the ratio of incidence below the age of 20 to that in the 20 to 34 age group is much smaller than in Rochester (2 : 1 in our material as compared to 5 : I in Rochester). This difference could perhaps be explained by the very small number of cases in the Rochester series. A question may be raised whether this finding is artifactual, due to incorrect population denominators. Indeed, our denominator is deficient in general, since it doesn’t account for either artificial or natural abortions. The number of abortions below the age of 20 may well have increased in recent years, causing a reIativeIy more pronounced deficiency in the denominator than in subsequent age groups. Still, Slocumb and Lund did take abortions into consideration. There-
Asia and Africa No. 25 59 49 36 25 29 9 23”
Rate 1.0 0.7 0.6 0.6 0.9 3.3 3.8 0.8
Israel No.
1 Rate
44; 26 13 3
0.7 1.1 0.8 1.1 0.8
1 1
7.7
90
1.0
Unknown (No.1
1 Rats 0.0 1.5 0.7 0.6 1.1 3.4 6.0
1 9 8 3 3
1.2
28
Table IV. Mean annual incidence of hydatidiform mole among Jewish women Israel per 1,000 live births, by age group and place of birth (1955 to 1965) Total
111
__-5+
14 11 16 11 4 4
4 31 29 9 z
mole
women in
3-4
0.6 0.7 0.6 0.5 0.3 3.0 31.3
1.2 1.0 0.7 0.7 0.8 1.7 11.1
hydatidiform
deliveries
2
1 Rate
of
mole among Jewish (1955 to 1965)
No. Total
aspects
2 :!
in
Unknown (No.) 3 5 5 6 3 ._ 2 2 26
fore, one might postulate a new environmental factor which affects primarily younger women. It would be of interest to see in the future to what extent this effect is associated with this specific cohort rather than with age. If the increase is associated with the cohort it should appear in the 20 to 24 age group in the 1966 to 1970 period. The marked increase beyond the age of 40 raises an analogy to similar findings in mongolism.15 This would also be consistent with the hypothesis relating hydatidiform mole to chromosomal aberrations’16 or to a defective ovum.17 Ethnic differences in the incidence of HM per live births were not observed in Israel except in the oIdest age group, in spite of the marked difference in the socioeconomic status between the Europeanand AsianAfrican-born women. The only difference
112
Matalon
and
Modan Am.
observed among the ethnic groups was the markedly higher incidence in European-born women age 45 and above. A possible explanation might be a considerably higher proportion of European-born women beyond the age of 40 who interrupt an unwanted pregnancy (abortion, while illegal, is easily available in Israel). Consequently, the denominator for this group, which includes a very small number of births, may be biased. Recurrency was believed to be rare on the basis of a review by Chesley and colleaguesl* who found only 39 such cases in the literature prior to 1946. However, in more recent reports, Acosta-Sison I9 found about one re-
January J. Obstet.
1, 1972 Gynecol.
current mole for every 50 moles, while Yen and MacMahong found a ratio of 1:35. A ratio of about 1:50 was found in our data. Since the risk observed for a first HM is about 1: 1,000 live births, this ratio indicates a considerably increased risk among wumen who had HM of developing another one. This is especially underscored by the fact that only one of the 9 women had a pregnancy between the 2 moles. The assistance of Mrs. Batia Paz, Mrs. Michaela Modan, and Miss Martha Klapp, as well as the Medical Record Librarians in all general hospitals in Israel, is greatly appreciated.
REFERENCES
1. Acosta-Sison, 2.
1959. Wei,
H.:
Philipp.
J.
Surg.
14:
290,
Lund, C. J.: AM. J. 104: 421, 1969. Westerhout, F. Cl., Jr., Morel, E. S., and Slate, W. G.: Ax J. OBSTET. GYNECOL. 103: 56, i969. Fernandes, M., and Marques, Cl.: Rev. Gynecol. Obstet. 100: 15. 1957. Aust. N. Z. J. Obstet. Steigrad, S. J.: Gynaecol. 9: 100, 1969. Sigler, A. T., Lilienfeld, A, M., Cohen, B. H., and Westlake, J. E.: Johns Hopkins Med. J. 117: 374, 1965. Makino, S., Sasaki, M. S., and Fukuschima, T.: Lancet 2: 1273, 1964. Hertig, A. T., and Edmonds, H. W.: Arch. Pathol. 30: 260, 1940. Chesley, L. C., Cosgrove, S. A., and Preece, J.: AM. J. OBSTET. GYNECOL. 52: 311, 1946. Acosta-Sison, H.: AM. J. OBSTET. GYNECOL. 78: 876, 1959. Slocumb,
OBSTET.
Ouyang, P. Cl.: AM. J. 85: 844, 1963. 3. Chun, D., Braga, Cl., and Lok, L.: J. Obstet. Gynaecol. Br. Commonw. 71: 185, 1964. 4. Poen, H. T., and Djojopranoto, M.: AM. J. OBSTET. GYNECOL. 92: 510, 1965. 5. Marquez-Monter, H., de la Vega, G. A., Robles, M., and Bolio-Cicero, A.: AM. J. ORSTET. GYNECOL. 85: 856, 1963. 6. Park, W. W.: J. Obstet. Gynaecol. Br. Commonw. 69: 637, 1962. I., and Dougherty, C. M.: Obstet. 7. Reiner, Gvnecol. 15: 735. 1960. M. A., Pomerance, W., and Mackles, a. Schiffer, A.: AM. J. OBSTET. GYNECOL. 80: 516, 1960. B.: AM. J. OBBTET. 9. Yen, S., and MacMahon, GYNECOL. 101: 126, 1968. 10. McCorriston, C. C.: AM. J. OBSTET. GYNECOL. 101: 377, 1968. OBSTET.
11.
P.
Y.,
and
12.
GYNECOL.
13. 14. 15.
16. 17. 18. 19.
J.
C.,
GYNECOL.
and
mole in
Israel MEIR
MATALON,
BARUCH Tel
M.D.*
MODAN,
Hashomer,
M.D.
I.rrael
A study based on all 534 newly diagnosed cases of hydatidiform mole in ]ewish women in Israel between 1950 and 1965 revealed a mean annual incidence of I :I,300 births. Incidence was relatively higher beyond the age of 40, independent of jarity. There were no interethnic differences except for a higher incidence in European-born women, 45 years of age and older. The risk of developing a second hydatidiform mole was about 20 times higher than for the first one. The incidence rose from I :2,400 births in 1950 to 1954 to 1:900 births in 1960 to 1965. This increase consisted of two components:(1) an increase in incidence in the 15 to 19 year age group, present in all ethnic categories, but limited to the more recent time period (1960 to 1965); (2) a marked increase in incidence in the 45+ age group from 1955 onward, primarily among European-born women.
1965 where no relation to socioeconomicstatus was observed, although some condition specific to the Far East might be responsible.g It is difficult to evaluate the meaning of variation in incidence observed for NM’s On the one hand, many patients with HM do not reach a hospital, many others are misdiagnosed,and the degree of recognition is correlated with the quality of medical care. On the other hand, in underdeveloped areas it is probable that a patient with HM has more chance to be hospitalized than one with a normal pregnancy, and, since data are based on hospital population, this will result in a high ratio to live births. In the present study, based on a nationwide record search, an attempt was made to assessto what extent the diseaseincidence differs among the main Israeli ethnic groups, which vary considerably in socioeconomic status but benefit from equally availabIe adequate medical care. A number of other
T H E M A R K E D variation in the incidence of hydatidiform mole (HM) between developed and underdeveloped countries1-9implies an environmental factor in the etiology of the disease. The highest frequencies have been described in the Far East, starting from 1: 125 births,3 and the lowest, 1:2,500, in Europe6 and the United States.7 The high frequency in Asia has been occasionally related to undernutrition, for instance, in the Philippines,l and in Hong Kong.3 This hypothesis was objected to by McCorriston*O on the basis of 94 HM casesin Hawaii between 1951 and From the Department of Clinical Efiidemiology, Tel Hashomer Government Hospital. The study wassupported by Research Agreement No. 06-125-2 from the United States Public Health Service. Received
for publication
April
21, 1971.
*This report is part of an M.D. thesis submitted by Dr. Matalon to the Hebrew University Medical School, Jerusalem, Israel. 107
108
Matalon
and
parameters of also studied. Materials
January Am. J. Obstet.
Modan
epidemiologic
and
interest
were
methods
The study was based on all cases of HM diagnosed in Israel between 1950 and 1965. Cases were ascertained through the medical record room listings of all general hospitals in Israel and gynecologic and/or obstetric specialty hospitals. Where no diagnostic listing was available in the hospital, a screening of the operating room records was made. Finally, a screening was made of the diagnostic listings in those departments of pathology where such a list was available. Arab women were excluded due to a lower rate of referral to hospitals. The criteria for inclusion of cases were based primarily on histologic diagnosis of HM by the individual pathologist in each hospital. Histologic confirmation was obtained in 99.2 per cent of the cases (95.2 per cent in the 1950 to 1954 time period and 99.8 per cent subsequently). The population figures were based on the 1961 census and subsequent estimates. Some of the computations were done with the aid of an IBM 360 computer. Results
Incidence. There
were 534 new cases of HM among Jewish women in Israel during this time period, including 12 women with recurrences. The mean annual incidence in the total period from 1950 to 1965 was 3.9 per 100,000 Jewish women or 7.9 per 100,000 women in the fertile age group (15 to 49). If the rate is computed on the basis of the number of live births, a rate of 0.75 per 1,000 live births or 1: 1,300 births is obtained. A more than twofold increase in incidence of HM was noted during the study period, from 0.41 per 1,000 live births (1: 2,400) in 1950 to 1954 to 0.69 (1: 1,500) in 1955 to 1959 and 1.06 (1:900) in 1960 to 1965 (Table I) . This increase is significant (p [p = 0] < 0.01). A similar trend of increase in incidence with time was also found in two hospitals in Boston.D The
1, 1972 Gynecol.
Table I. Mean annual incidence of hydatidiform mole among Jewish women in Israel ( 1950 to 1965) by chronologic time period Time
period
1950 - 1954 1955 - 1959 1960 - 1965
No.
of
87 150 297
cases
Rate/l,000 live births 0.41 0.69 1.06
marked increase in the observed incidence during the observed time periods could be related in part to a better awareness on the part of the population of the need to consult a gynecologist in the case of unexpected bleeding and of the physicians to look for a HM in each abortion case. However, a comparison of the incidence in the 3 time periods by age (Fig. 1) reveals that the increase with time is primarily due to two components : ( 1) an increase in the over 40 age groups in the 1955 to 1965 period, and (2) the appearance of an additional peak in the youngest age group ( 15 to 19) in 1960 to 1965. Of the two components, only the increase in older age which started in 1955 can be reasonably accounted for by better recognition. With regard to the 15 to 19 group, better recognition seems to be an insufficient explanation, because of its beonly after 1960. It is of lated appearance, interest that this recent appearance of a relatively increased incidence in the 15 to 19 age group, which is significantly different from the previous time period (p [Poisson] < 0.05), is consistent with the findings of Slocumb and Lund,‘l who indicated a similar trend in the disease incidence in younger age groups in the Rochester, New York, area. Since it seems that information regarding HM is incomplete for the earlier time period, further analysis will be limited to cases diagnosed during 1955 to 1965. Age. If age-specific incidence rates are computed on the basis of female population, peak incidence rates seem to occur in the 20 to 29 age group (Table II). But, if the rates are computed on the basis of births, incidence rates are about the same below the age of
Volume
112
Number
1
Epidemiologic
*("
54
to
IS
#
1s
aspects
40
of hydatidiform
45
mole
109
4 50
AEf
Fig. 1. Comparison of mean annual age-specific rates of hydatidiform women in Israel per 1,000 live births in 3 chronologic time periods. 40 with a subsequent increase, particularly beyond the age of 45. The rate for the 40 to 44 age group is significantly different (p [Poisson] < 0.05) from both the rates for the age groups above and below. This indicates that the peak in the 20 to 29 age group, observed in the rates based on the total fertile female population, is related to the higher fertility of this age group. Parity. Because of the obvious correlation between the woman’s age and the number of previous births, the factor of parity has to be examined separately. This is presented in Table III. It is evident that incidence rate
mole among Jewish
in each age group, including the increased rate beyond the age of 40, is independent of the number of previous deliveries, i.e., there are no significant differences in the rates ‘among parity groups. Consequently, parity does not seem to play a role in the disease etiology. Ethnic origin. If incidence rates are computed on the basis of the total female population in the fertile age, an apparently higher rate is present in all age groups among the Asian and African born as compared to the European born. However, because of the difference in fertility between the ethnic groups,
110
Matalon
and Modan Am.
i.e., a lower fertility rate among the European born, this comparison is invalid. Incidence rates by ethnic group based on the number of births do not reveal significant differences between the ethnic groups except for a markedly higher incidence in European-born women age 45 and over, as compared to the Asian-African and Israeli groups (p [ Poisson] < 0.05) (Table IV). The higher incidence in older European women is independent of parity since it is present in each parity group. Recurent mole. Eleven of the women had a recurrent mole during the study period. Of the 447 cases first diagnosed in the 1955 to 1965 period, for which better information is available, there were 9 recurrent cases. This yields a ratio of 1:50, i.e., about 20 times higher than the observed rate of 1: 1,100 live births for this period. The risk of a recurrent mole was smaller if normal deliveries had occurred in the intervening period. Thus, it is of interest that in 7 of the 9 women the second mole occurred within one year of the previous mole. In another woman the difference was 9 years but with a history of 4 abortions and no norma1 delivery. The patient was the only one who had a normal delivery in the two intervening years between the two moles. Comment The incidence of hydatidiform mole in Israeli Jewish women is in the same range as that in Western Europe and the United States.6-8 A similar incidence (1: I,1 15) was found in Los Angeles I2 for the 1950 to 1964 period, in BraziP (1: 1,071) in the 1951 to 1957 period, and in Australia14 (1: 962) for the years 1950 to 1966. In order to evaluate any trends correctly, incidence should be computed on the basis of live births and not on the basis of the female population. Otherwise, a more fertile group will present a higher incidence than a less fertile one, even when no difference in the risk of a woman to develop HM exists. For instance, it has been emphasized in some publications that the disease is most frequent in the third decade of Iife3-5r 7 and
January J. Obstet.
1, 1972 Gynecol.
Table II. Mean annual incidence of hydatidiform mole among Jewish women in Israel ( 1955 to 1965) per 100,000 women and per 1,000 live births, by age group Age &PUP 15-19 20-24 25-29 30-34 35-39 40-44 45+ Unknown
No. of Rate/lOO,OOO cases women+ 39 124 95 68 47 40 31 3
Totals
447
“In this only once.
computation
iDenominator
is women
Rate/l,000 live births
4.5 17.2 13.0 9.2 6.9 Et
1.1 0.8 0.6 0.7 1.0 3.2 11.3
8.9 recurrent age 45
0.9 cazes
were
considered
to 49.
that it is more prevalent among parous women.3y 5a 7 In our data, a peak in the 20 to 29 year age group and a parity effect could be observed which were solely associated with a larger number of births. When rates are computed per live births, a completely different age effect is noted; there are two peaks, a small one below the age of 20 and a marked one beyond the age of 40. Birth order in itself was not found to have any effect. Yen and MacMahonD could find no significant effect of parity either. The higher incidence in the 15 to 19 year age group in the more recent period from 1960 to 1965 is in line with the findings by Slocumb and Lundll on the basis of 18 cases diagnosed at Strong Memorial Hospital in Rochester, New York, and also noted in the study by Westerhout and associatesI from Los Angeles. Slocumb and Lund emphasize that the increase in the young age group is a recent phenomenon. They try to relate this increase to more frequent sexual intercourse in younger age groups in recent years. It does not seem plausible, however, that this would explain the higher incidence compared to the 20 to 34 year age group. Our findings are consistent with the notion that this is a relatively recent phenomenon; in 1950 to 1954 and 1955 to 1959 the incidence in the 15 to 19 year age group was similar to the following age groups up to the age
Volume Number
112 1
Epidemiologic
Table III. Mean annual incidence of hydatidiform Israel per 1,000 live births, by age group and parity
Age
group
< 20 20-24 25-29 30-34 35-39 40-44 45+ Unknown
No. 39 124 95 68 47 40 31 3
Totals
477
0
) Rate
No.
1.1 0.8 0.6 0.7 1.0 3.2 11.3
34 62 18 6 2 1 1
0.9
124
of previous
1
( Rate
No.
No.
( Rate
No.
1 Rate
4
0.0 0.7 0.4 0.8 1.5 3.0 33.3
5 16 16 7 7 8
0.0 0.4 0.5 0.8 0.8 3.3 ..i... ‘)‘,3
82
0.6
60
0.8
59
0.8
0.9
No. 3 13 18 22 25 12 1 94
Europe and America
Age
group
< 20 20-24 25-29 30-34 35-39 40-44 45+ Unknown Totals
No. 39 124 95 68 47 40 31 3 447
Rate
Rate
No.
1.1 0.8 0.6 0.7 1.0 3.2 11.2
7 18 15 13 16 :i
0.9
99
1.5 0.7 0.4 0.5 1.1 6;::
0.9
of 40, and only in 1960 to 1965 did a relatively increased incidence appear. On the other hand, the ratio of incidence below the age of 20 to that in the 20 to 34 age group is much smaller than in Rochester (2 : 1 in our material as compared to 5 : I in Rochester). This difference could perhaps be explained by the very small number of cases in the Rochester series. A question may be raised whether this finding is artifactual, due to incorrect population denominators. Indeed, our denominator is deficient in general, since it doesn’t account for either artificial or natural abortions. The number of abortions below the age of 20 may well have increased in recent years, causing a reIativeIy more pronounced deficiency in the denominator than in subsequent age groups. Still, Slocumb and Lund did take abortions into consideration. There-
Asia and Africa No. 25 59 49 36 25 29 9 23”
Rate 1.0 0.7 0.6 0.6 0.9 3.3 3.8 0.8
Israel No.
1 Rate
44; 26 13 3
0.7 1.1 0.8 1.1 0.8
1 1
7.7
90
1.0
Unknown (No.1
1 Rats 0.0 1.5 0.7 0.6 1.1 3.4 6.0
1 9 8 3 3
1.2
28
Table IV. Mean annual incidence of hydatidiform mole among Jewish women Israel per 1,000 live births, by age group and place of birth (1955 to 1965) Total
111
__-5+
14 11 16 11 4 4
4 31 29 9 z
mole
women in
3-4
0.6 0.7 0.6 0.5 0.3 3.0 31.3
1.2 1.0 0.7 0.7 0.8 1.7 11.1
hydatidiform
deliveries
2
1 Rate
of
mole among Jewish (1955 to 1965)
No. Total
aspects
2 :!
in
Unknown (No.) 3 5 5 6 3 ._ 2 2 26
fore, one might postulate a new environmental factor which affects primarily younger women. It would be of interest to see in the future to what extent this effect is associated with this specific cohort rather than with age. If the increase is associated with the cohort it should appear in the 20 to 24 age group in the 1966 to 1970 period. The marked increase beyond the age of 40 raises an analogy to similar findings in mongolism.15 This would also be consistent with the hypothesis relating hydatidiform mole to chromosomal aberrations’16 or to a defective ovum.17 Ethnic differences in the incidence of HM per live births were not observed in Israel except in the oIdest age group, in spite of the marked difference in the socioeconomic status between the Europeanand AsianAfrican-born women. The only difference
112
Matalon
and
Modan Am.
observed among the ethnic groups was the markedly higher incidence in European-born women age 45 and above. A possible explanation might be a considerably higher proportion of European-born women beyond the age of 40 who interrupt an unwanted pregnancy (abortion, while illegal, is easily available in Israel). Consequently, the denominator for this group, which includes a very small number of births, may be biased. Recurrency was believed to be rare on the basis of a review by Chesley and colleaguesl* who found only 39 such cases in the literature prior to 1946. However, in more recent reports, Acosta-Sison I9 found about one re-
January J. Obstet.
1, 1972 Gynecol.
current mole for every 50 moles, while Yen and MacMahong found a ratio of 1:35. A ratio of about 1:50 was found in our data. Since the risk observed for a first HM is about 1: 1,000 live births, this ratio indicates a considerably increased risk among wumen who had HM of developing another one. This is especially underscored by the fact that only one of the 9 women had a pregnancy between the 2 moles. The assistance of Mrs. Batia Paz, Mrs. Michaela Modan, and Miss Martha Klapp, as well as the Medical Record Librarians in all general hospitals in Israel, is greatly appreciated.
REFERENCES
1. Acosta-Sison, 2.
1959. Wei,
H.:
Philipp.
J.
Surg.
14:
290,
Lund, C. J.: AM. J. 104: 421, 1969. Westerhout, F. Cl., Jr., Morel, E. S., and Slate, W. G.: Ax J. OBSTET. GYNECOL. 103: 56, i969. Fernandes, M., and Marques, Cl.: Rev. Gynecol. Obstet. 100: 15. 1957. Aust. N. Z. J. Obstet. Steigrad, S. J.: Gynaecol. 9: 100, 1969. Sigler, A. T., Lilienfeld, A, M., Cohen, B. H., and Westlake, J. E.: Johns Hopkins Med. J. 117: 374, 1965. Makino, S., Sasaki, M. S., and Fukuschima, T.: Lancet 2: 1273, 1964. Hertig, A. T., and Edmonds, H. W.: Arch. Pathol. 30: 260, 1940. Chesley, L. C., Cosgrove, S. A., and Preece, J.: AM. J. OBSTET. GYNECOL. 52: 311, 1946. Acosta-Sison, H.: AM. J. OBSTET. GYNECOL. 78: 876, 1959. Slocumb,
OBSTET.
Ouyang, P. Cl.: AM. J. 85: 844, 1963. 3. Chun, D., Braga, Cl., and Lok, L.: J. Obstet. Gynaecol. Br. Commonw. 71: 185, 1964. 4. Poen, H. T., and Djojopranoto, M.: AM. J. OBSTET. GYNECOL. 92: 510, 1965. 5. Marquez-Monter, H., de la Vega, G. A., Robles, M., and Bolio-Cicero, A.: AM. J. ORSTET. GYNECOL. 85: 856, 1963. 6. Park, W. W.: J. Obstet. Gynaecol. Br. Commonw. 69: 637, 1962. I., and Dougherty, C. M.: Obstet. 7. Reiner, Gvnecol. 15: 735. 1960. M. A., Pomerance, W., and Mackles, a. Schiffer, A.: AM. J. OBSTET. GYNECOL. 80: 516, 1960. B.: AM. J. OBBTET. 9. Yen, S., and MacMahon, GYNECOL. 101: 126, 1968. 10. McCorriston, C. C.: AM. J. OBSTET. GYNECOL. 101: 377, 1968. OBSTET.
11.
P.
Y.,
and
12.
GYNECOL.
13. 14. 15.
16. 17. 18. 19.
J.
C.,
GYNECOL.
and