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Prognosis of a new pregnancy following previous spontaneous abortions
European Journal of Obstetrics & Gynecology and Reproductive 0 1991 Elsevier Science Publishers B.V. (Biomedical Division)
EUROBS
Biology, 39 (1991) 31-36 0028-2243/91/$03.50
31
01076
Prognosis of a new pregnancy following previous spontaneous abortions Ulla Breth Knudsen ‘, Villy Hansen ‘, Svend Juul 2 and Niels Jmgen Secher ’ ’ Department of Gynaecology and Obstetrics, Rrhus Municipal Hospital and ’ Institute of Social Medicine, (inrcersrtv of Arhus, .&hus, Denmark Accepted
for publication
14 May 1990
Summary The risk for a clinical spontaneous abortion in a pregnancy following 0 to 4 consecutive spontaneous abortions was estimated in a large, unselected, Danish population, including approximately 300500 pregnancies. The overall risk for spontaneous abortion was 11% and the risk for a spontaneous abortion was 16, 25, 45 and 54% after 1 to 4 previous consecutive spontaneous abortions, respectively. For women over 35 years, the risk for spontaneous abortion was significantly increased, but the almost identical abortion rates after repeated abortions in both young and old women indicate a risk factor which is not age-related. Spontaneous
abortion;
Recurrent
consecutive
abortion;
Habitual
Introduction For some women (around 5% of women in the reproductive age) clinical spontaneous abortion is a recurring problem, and information about the prognosis for the following pregnancies is extremely important when counselling these women/couples. The overall risk of spontaneous abortion is generally accepted to be approximately 15% [l]. Increase in the risk of abortion after a previous abortion is reported consistently [2-51, but the
Correspondence: N.J. Secher, Obstetrics, Arhus Municipal mark.
Department of Gynaecology and Hospital, 8000 Arhus C, Den-
abortion
reported risks of recurrence differ considerably (see Table I), and no generally accepted figures are available. This variation is presumably due to differences in definition of spontaneous abortion. selection of patients and the data collecting method. Furthermore, the number of patients involved is often small, which consequently gives broad confidence limits. Maternal age is positively correlated to abortion risk [4,6], but the confounding effect of gravidity is still debated [3,5,7]. The aim of the present study, which is based on a large, unselected population, is to estimate the risk for clinical spontaneous abortion in a pregnancy following 0 to 4 consecutive spontaneous abortions, and to study the influence of maternal age.
32
previous consecutive spontaneous abortions since 1977 was determined, and the risk of spontaneous abortion for the study pregnancies was estimated. As an example the risk of a third spontaneous abortion was determined by dividing the total number of women experiencing a third consecutive abortion with the total number of women with a third pregnancy ending in a spontaneous abortion or birth in the period 1980-1984. Due to restricted computer capacity, the overall risk and the risk for women with no prior spontaneous abortions was determined from a 6.6% representative sample of pregnancies, whereas the risk after one or more spontaneous abortions was determined without sampling. A validation study was carried out by comparing the information from the DNPR with discharge summaries on the 406 admissions following three or more spontaneous abortions. Chi-square and Chi-square for trend [9] were used for statistical evaluation. Confidence limits were calculated according to the binomial distribution.
Materials and Methods
This study is based upon data from The Danish National patient Register (DNPR) (Landspatientregisteret), which since January 1977 has registered discharge diagnoses for patients admitted to all hospitals in Denmark (except .diagnoses for mental diseases). The primary material included 761464 discharges with one or more pregnancy-related diagnoses (ICD8, Danish version, Number 630-678, [8]) during the period 1977-1984. The discharge diagnoses were classified as (1) pregnancy terminated by spontaneous abortion (ICD8 643-645); (2) pregnancy terminated by birth (ICD8 650-662); or (3) other pregnancy-related conditions, including induced abortions. This last group was not included in the analysis. The admission date was considered the date of birth or spontaneous abortion. Admissions less than 8 weeks after a spontaneous abortion and within 40 weeks prior to a birth were eliminated, as they were assumed to represent complications of abortion or pregnancy rather than a terminating event. Spontaneous abortion was defined as pregnancy loss before 28 weeks of gestation. The study pregnancies were pregnancies ending in birth or spontaneous abortion during 1980-1984. For each of the 300500 study pregnancies the number of TABLE
Results The study included approximately 300 500 study pregnancies, of which about 33900 were spontaneous abortions during the 5 years of observation.
I
Risk of subsequent Author
Malpas (1938) Goldziehei and Ben&no (1958) Warburton and Fraser (1964) Leridon (1976) Poland et al. (1977) Naylor and Warburton (1979) Parazzini (1988) Regan (1988)
pregnancy
ending No. of pregnancies observed
5432 638 14000 66 226
in spontaneous
abortion
Number 0
12 15
(X)
of previous
abortions
Comments
1
2
3
4
22
38
73
94
23
24
40
24 22 19
26 35 35
32
26
47
23
29 20 29
33 40 36
12
C, consecutive spontaneous abortions; NC, non-consecutive spontaneous studies; T, theoretical calculations; *, data obtained by interviews.
abortions;
>4 T 3x
R NC * C C* C* P
54
P, prospective
study;
R, review of previous
33 TABLE
II
TABLE
Risk of subsequent tion
pregnancy
ending
in a spontaneous
No. of previous abortions
Number of pregnancies studied
Abortion
0 1 2 3 4
18164 a 21054 2231 353 94
10.7 15.9 25.1 45.0 54.3
Overall
19,737 ‘I
11.3 (10.9-11.8)
abor-
risk of abortion,
(%) (10.3-11.2) (15.4-16.4) (23.4-27.0) (39.8-50.4) (43.7-64.4)
according
to age of mother
Age of mother
Number of pregnancies
Spontaneous ahortions (Z)
-19 20-29 30-34 35-39 40+
1105 13173 3 900 1299 260
10.8 (9.0- 12.7) 9.7 (9.2- 12.7) 11.5 (10.6-12.6) 21.4(19.2-23.7) 42.2 (35.1-47.4)
Overall
19737
11.3(10.9-11.x)
risk
The table is calculated from a 6.65 \.unplc pregnancies. Figures in brackets: 95% confidence limits. x2 (trend)=244; df =l; P~O.0001.
” A 6.6% sample of the study pregnancies. Figures in brackets: 95% confidence limits. x2 (trend) = 728; d/=1; P < 0.0001.
The risk of spontaneous abortion related to the number of previous consecutive spontaneous abortions is presented in table II. The overall risk of a pregnancy ending as a spontaneous abortion was 11.3%, versus 10.7% for women with no prior spontaneous abortions. For a pregnancy following one prior spontaneous abortion the risk of spontaneous abortion increased to 15.9%. For pregnancies following 2, 3 and 4 consecutive spontaneous abortions, the risk of spontaneous abortion was 25.1, 45.0, and 54.3%, respectively. The increased risk according to the number of preceding spontaneous abortions was highly significant.
TABLE
Overall
III
The overall risk of spontaneous abortion was significantly related to maternal age, as shown in Tables III and IV, with a low risk for women under 35 years, but a much higher risk for older women. Table IV also shows that the abortion risk for older women with no previous abortion is high, but the rise in risk according to the number of previous spontaneous abortions is less than for younger women. There was no significant time trend during the study period in the overall risk of abortion. nor in the risk of abortion in any subgroup. In order to validate the information from DNPR, we attempted to review the discharge
IV
Risk of spontaneous Number of previous abortions
abortion.
according
to number
of previous
Age -C 35
consecutive
spontaneous
abortions
in relation
IO maternal
Age 2 35
”
risk (W)
n
risk (%)
1 2 3 4
16 806 a 18749 1908 291 78
9.7 14.9 23.8 43.0 53.8
1358 a 2 305 323 62 16
24.2 24.0 32.8 54.8 56.3
Overall
18178 a
10.2
1559 a
24.7 (22.6-26.9)
0
of the study
a A 6.6%sample of the study pregnancies. n. number of study pregnancies in subgroup. Figures in brackets : 95% confidence limits. Age c 35: x2 (trend) = 655; d/= 1; P < 0.0001. Age 3 35: x2 (trend) = 23.3: df= 1: P < 0.0001.
(9.2-10.1) (14.3-15.4) (21.9-25.8) (37.2-48.9) (42.2-65.2) (9.7-10.6)
(22.0-26.6) (22.3-25.X) (27.7-38.2) (41.7-67.5) (29.9-80.2)
age
34 TABLE V Validation study: Comparison of DNPR diagnoses with discharge summaries. Admissions after at least three previous spontaneous abortions (SA) Diagnosis according to discharge summaries
Diagnosis according to DNPR Birth
SA
Total
Birth SA Not pregnant
205 0 0
0 166 35
205 166 35
Total
205
201
406
DNPR: The Danish National Patient Register.
summaries on 479 spontaneous abortions and births after three or more previous spontaneous abortions. 406 discharge summaries (85%) were reviewed, as six hospitals did not provide copies of the discharge summaries. The main results of the validation study are shown in Table V. There was no misclassification of births, but 17% of admissions classified as spontaneous abortion in DNPR were in fact not pregnancy related. The source of this misclassification was the discharge diagnosis ‘habitual abortion’ which in some cases represented an actual abortion, while in others cases it represented admission of a non-pregnant woman with the purpose of investigating the cause of previous spontaneous abortions. The information in DNPR did not enable us to correct this error systematically. Discussion
In Denmark almost all births (99.3% in 1981) and all induced abortions take place in hospitals or clinics and are consequently registered in The Danish National Patient Register. Births not giving rise to hospital admission are not accounted for, but are probably very rare among women with previous spontaneous abortions. The bias induced by omitting these cases is therefore small. The number of spontaneous abortions not registered is unknown, but it is assumed that the large majority of clinically manifest abortions give rise to hospital admission, as all women in Denmark with clinical abortion are offered evacuation.
As the purpose of this study was to estimate the prognosis of the following pregnancy only clinical abortions were included, as subclinical abortions mainly are regarded as an infertility problem. The central registration in DNPR may be disposed to some misclassification, in spite of WHO’s clear criteria for the classification of diseases [lo]. Induced abortion is permitted on demand during the first 12 weeks of pregnancy in Denmark, but must be performed in a hospital by law. Because of this, misclassification between induced and spontaneous abortions is small. According to Susser [ll] the existence of high rates of induced abortion in a population may distort the rate of spontaneous abortion. In Denmark the induced abortion rate is around 27% of all pregnancies. Applying Susser’s model, which assumes the spontaneous abortion rate to be identical in women, who intend to seek abortion and those who do not, the ‘true spontaneous abortion rate’ is the number of spontaneous abortions divided by the total number of spontaneous abortions, the number of births taking place after 28 weeks and one half of the number of induced abortions. In our study the ‘corrected’ overall spontaneous abortion rate would be 9.3% compared to the crude 11.3%. The correction is mainly of interest for the overall spontaneous abortion rate, as women with habitual abortion rarely have an induced abortion. Abortions prior to 1977 were not recorded, making the estimated prognosis of a new pregnancy with respect to the number of previous abortions too pessimistic. The purpose of restricting the material to pregnancies terminated during 1980 to 1984 was to reduce information bias by allowing for the recording of at least 3 years of abortion/ birth experience. As there was no significant time trend in the risk of abortion conditional on the number of recorded previous abortions, the restriction seems to have been successful. As one birth or spontaneous abortion can give rise to several admissions, it was necessary to formulate a set of rules for the interpretation of the information about the individual discharges as described above. The elimination of admissions too close to a birth or spontaneous abortion can give rise to misclassification in some extreme cases.
35
The direction of this bias can not be determined, but the magnitude is probably small. In the validation study we found no misclassification from this source. The validation study demonstrated an overestimation by 17% of spontaneous abortions in study pregnancies after three or more previous spontaneous abortions, due to ambiguous use in DNPR of the diagnosis ‘habitual abortion’. In the validated cases the risk of abortion for women with three or more previous spontaneous abortions was 49.5% according to DNPR, in contrast to 44.7% according to the discharge summaries. On the other hand, this type of misclassification has also given rise to overestimations of the number of previous spontaneous abortions. Misclassification of previous spontaneous abortions has not been investigated, but since the diagnosis ‘habitual abortion’ depends on at least two prior spontaneous abortions, it is probably of minor magnitude. Overall, misclassification due to ambiguous use of the diagnosis ‘habitual abortion’ in DNPR has probably given rise to a somewhat elevated
TABLE
VI
Assessment Source mation
of bias due to missing
of possible
Births outside
SAs not tal h
misinfor-
hospital
or misclassified
information
Consequences for estimation of study pregnancies Negligible underestimate number of study births
admitted
to hospi-
Minor underestimate ber of study SAs
Induced abortions fied as spontaneous
misclassiabortions
Negligible underestimate number of study SAs
Abortions recorded
estimate of the risk of spontaneous abortion, conditional on the number of previous spontaneous abortions. Table VI is an overall assessment of the magnitude and direction of bias in the estimate of the spontaneous abortion risk, conditional on the number of previous consecutive spontaneous abortions. It is concluded that the total effect of incomplete information is probably a moderate overestimation of the conditional abortion risk. The estimates calculated should therefore be considered slightly pessimistic. The overall risk of spontaneous abortion in this study, 11.3’%, is lower than previously reported (see Table I), with the exception of Regan [12]. She found in a prospective study in Cambridge, England (1986), an overall spontaneous abortion rate of 10.3% and 5.6% for primigravidae. The low estimate in Regan’s study might, however, be due to patient selection. The low incidence of spontaneous abortion in our unselected population could be due to the use of effective contraceptives, and the opportunity for induced abortion on demand,
prior
of
of num-
of
to 1977 not
Habitual abortion admissions misclassified as SAs
Major overestimate ber of study SAs
Overall
Moderate overestimate number of study SAs
Consequences for estimated conditional SA risk ’
Consequences for estimation of prior pregnancies
of num-
of
Negligible underestimate number of prior births
of
Negligible error known direction
Minor underestimate of number of prior consecutive SAs
Minor error rection
Negligible underestimate of number of prior consecutive SAs
Negligible direction
Minor underestimate of number of prior consecutive SAs
Minor
Moderate overestimate of number of prior consecutive SAs
Minor or estimate
Minor over- or underestimate of number of prior SAs
Moderate
of
of unknown
error
un-
di-
of unknown
overestimate
moderate
overestimate
a Conditional SA risk: Risk of SA in a study pregnancy after a given number of prior consecutive SAs. b The event of interest is clinical abortion. Early subclinical pregnancy loss is not within the scope of the investigation. SA, spontaneous abortion.
over-
36
which means that most pregnancies not terminated by induced abortion were wanted and, thereby presumably less prone to complications. Our results are estimated from a large, unselected population obtained from a central register (DNPR). Previous reports of the outcome of a pregnancy following one or more spontaneous abortions are mainly based on small and often highly selected groups of women (see Table I). Most information in these groups is obtained by interview, and therefore prone to recall bias [5]. The association between the age of the mother and the spontaneous abortion rate has been discussed [3,4,6]. Our results show that the spontaneous abortion rate is steady up to the age of 35 years, but then increases remarkably, reaching 41% when the mother is over 40 years old. The increase in the spontaneous abortion rate in relation to previous spontaneous abortions can not be explained by the increase in maternal age alone. Poland et al. [4] found a significant increased risk of spontaneous abortion for women over 35 years of age, whereas Parazzini [13] found no influence of the maternal age. Our study confirms an increase in abortion rate by age, but the almost identical abortion rates after several abortions in young and old women indicate a risk factor, which is not age-related. Acknowledgment
This report was supported financially by The Danish Medical Research Council. References 1 Huisjes HJ. Spontaneous Abortion. Edingburgh: Churchill Livingstone, 1984.
2 Goldzieher JW, Benign0 BB. The treatment of threatened and recurrent abortion: a critical review. Am J Obstet Gynecol 1958;75:1202-1214. 3 Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet 1964;16:1-25. 4 Poland BJ, Miller JR, Jones DC, Trimble BK. Reproductive counseling in patients who have had a spontaneous abortion. Am J Obstet Gynecol 1977;127:685-691. 5 Naylor AF, Warburton D. Sequential analysis of spontaneous abortion. II. Collaborative study data show that gravidity determines a very substantial rise in risk. Fertil Steril 1979;31:282-286. 6 Leridon H. Facts and artifacts in the study of intra-uterine mortality: a reconsideration from pregnancy histories. Population Studies 1976;30:319-335. 7 Kline J, Shrout PE, Stein ZA, Susser M, Weiss M. II. An epidemiological study of the role of gravidity in spontaneous abortion. Early Hum Dev 1978;1:345-356. 8 National Board of Health. Klassifikation af sygdomme, 8.revision 1965. Systematisk fortegnelse. Copenhagen, 1982. 9 Armitage P. Statistical methods in medical research. London: Blackwell Scientific Publications, 1974. 10 National Board of Health. Evaluering af Landspatientregisteret. En pilotundersegelse. Sygehusstatistik 1984;11:19. 11 Susser E. Spontaneous abortion and induced abortion: an adjustment for the presence of induced abortion when estimating the rate of spontaneous abortion from cross-sectional studies. Am J Epidemiol. 1983;117:305-308. 12 Regan L. A prospective study of spontaneous abortion. Early pregnancy loss: mechanisms and treatment. In: Beard RW, Sharp F (eds). Proceedings of the 18th study group of the Royal College of Obstetricians and Gynaecologists. 1988;23-37. 13 Parazzini F, Acaia B, Ricciardiello 0, Fedele L, Liati P, Candiani GB. Short-term reproductive prognosis when no cause can be found for recurrent miscarriage. Br J Obstet Gynaecol 1988;95:654-658. 14 Malpas P. A study of abortion sequences. J Obstet Gynaecol Br Emp 1938;45:932-949.
EUROBS
Biology, 39 (1991) 31-36 0028-2243/91/$03.50
31
01076
Prognosis of a new pregnancy following previous spontaneous abortions Ulla Breth Knudsen ‘, Villy Hansen ‘, Svend Juul 2 and Niels Jmgen Secher ’ ’ Department of Gynaecology and Obstetrics, Rrhus Municipal Hospital and ’ Institute of Social Medicine, (inrcersrtv of Arhus, .&hus, Denmark Accepted
for publication
14 May 1990
Summary The risk for a clinical spontaneous abortion in a pregnancy following 0 to 4 consecutive spontaneous abortions was estimated in a large, unselected, Danish population, including approximately 300500 pregnancies. The overall risk for spontaneous abortion was 11% and the risk for a spontaneous abortion was 16, 25, 45 and 54% after 1 to 4 previous consecutive spontaneous abortions, respectively. For women over 35 years, the risk for spontaneous abortion was significantly increased, but the almost identical abortion rates after repeated abortions in both young and old women indicate a risk factor which is not age-related. Spontaneous
abortion;
Recurrent
consecutive
abortion;
Habitual
Introduction For some women (around 5% of women in the reproductive age) clinical spontaneous abortion is a recurring problem, and information about the prognosis for the following pregnancies is extremely important when counselling these women/couples. The overall risk of spontaneous abortion is generally accepted to be approximately 15% [l]. Increase in the risk of abortion after a previous abortion is reported consistently [2-51, but the
Correspondence: N.J. Secher, Obstetrics, Arhus Municipal mark.
Department of Gynaecology and Hospital, 8000 Arhus C, Den-
abortion
reported risks of recurrence differ considerably (see Table I), and no generally accepted figures are available. This variation is presumably due to differences in definition of spontaneous abortion. selection of patients and the data collecting method. Furthermore, the number of patients involved is often small, which consequently gives broad confidence limits. Maternal age is positively correlated to abortion risk [4,6], but the confounding effect of gravidity is still debated [3,5,7]. The aim of the present study, which is based on a large, unselected population, is to estimate the risk for clinical spontaneous abortion in a pregnancy following 0 to 4 consecutive spontaneous abortions, and to study the influence of maternal age.
32
previous consecutive spontaneous abortions since 1977 was determined, and the risk of spontaneous abortion for the study pregnancies was estimated. As an example the risk of a third spontaneous abortion was determined by dividing the total number of women experiencing a third consecutive abortion with the total number of women with a third pregnancy ending in a spontaneous abortion or birth in the period 1980-1984. Due to restricted computer capacity, the overall risk and the risk for women with no prior spontaneous abortions was determined from a 6.6% representative sample of pregnancies, whereas the risk after one or more spontaneous abortions was determined without sampling. A validation study was carried out by comparing the information from the DNPR with discharge summaries on the 406 admissions following three or more spontaneous abortions. Chi-square and Chi-square for trend [9] were used for statistical evaluation. Confidence limits were calculated according to the binomial distribution.
Materials and Methods
This study is based upon data from The Danish National patient Register (DNPR) (Landspatientregisteret), which since January 1977 has registered discharge diagnoses for patients admitted to all hospitals in Denmark (except .diagnoses for mental diseases). The primary material included 761464 discharges with one or more pregnancy-related diagnoses (ICD8, Danish version, Number 630-678, [8]) during the period 1977-1984. The discharge diagnoses were classified as (1) pregnancy terminated by spontaneous abortion (ICD8 643-645); (2) pregnancy terminated by birth (ICD8 650-662); or (3) other pregnancy-related conditions, including induced abortions. This last group was not included in the analysis. The admission date was considered the date of birth or spontaneous abortion. Admissions less than 8 weeks after a spontaneous abortion and within 40 weeks prior to a birth were eliminated, as they were assumed to represent complications of abortion or pregnancy rather than a terminating event. Spontaneous abortion was defined as pregnancy loss before 28 weeks of gestation. The study pregnancies were pregnancies ending in birth or spontaneous abortion during 1980-1984. For each of the 300500 study pregnancies the number of TABLE
Results The study included approximately 300 500 study pregnancies, of which about 33900 were spontaneous abortions during the 5 years of observation.
I
Risk of subsequent Author
Malpas (1938) Goldziehei and Ben&no (1958) Warburton and Fraser (1964) Leridon (1976) Poland et al. (1977) Naylor and Warburton (1979) Parazzini (1988) Regan (1988)
pregnancy
ending No. of pregnancies observed
5432 638 14000 66 226
in spontaneous
abortion
Number 0
12 15
(X)
of previous
abortions
Comments
1
2
3
4
22
38
73
94
23
24
40
24 22 19
26 35 35
32
26
47
23
29 20 29
33 40 36
12
C, consecutive spontaneous abortions; NC, non-consecutive spontaneous studies; T, theoretical calculations; *, data obtained by interviews.
abortions;
>4 T 3x
R NC * C C* C* P
54
P, prospective
study;
R, review of previous
33 TABLE
II
TABLE
Risk of subsequent tion
pregnancy
ending
in a spontaneous
No. of previous abortions
Number of pregnancies studied
Abortion
0 1 2 3 4
18164 a 21054 2231 353 94
10.7 15.9 25.1 45.0 54.3
Overall
19,737 ‘I
11.3 (10.9-11.8)
abor-
risk of abortion,
(%) (10.3-11.2) (15.4-16.4) (23.4-27.0) (39.8-50.4) (43.7-64.4)
according
to age of mother
Age of mother
Number of pregnancies
Spontaneous ahortions (Z)
-19 20-29 30-34 35-39 40+
1105 13173 3 900 1299 260
10.8 (9.0- 12.7) 9.7 (9.2- 12.7) 11.5 (10.6-12.6) 21.4(19.2-23.7) 42.2 (35.1-47.4)
Overall
19737
11.3(10.9-11.x)
risk
The table is calculated from a 6.65 \.unplc pregnancies. Figures in brackets: 95% confidence limits. x2 (trend)=244; df =l; P~O.0001.
” A 6.6% sample of the study pregnancies. Figures in brackets: 95% confidence limits. x2 (trend) = 728; d/=1; P < 0.0001.
The risk of spontaneous abortion related to the number of previous consecutive spontaneous abortions is presented in table II. The overall risk of a pregnancy ending as a spontaneous abortion was 11.3%, versus 10.7% for women with no prior spontaneous abortions. For a pregnancy following one prior spontaneous abortion the risk of spontaneous abortion increased to 15.9%. For pregnancies following 2, 3 and 4 consecutive spontaneous abortions, the risk of spontaneous abortion was 25.1, 45.0, and 54.3%, respectively. The increased risk according to the number of preceding spontaneous abortions was highly significant.
TABLE
Overall
III
The overall risk of spontaneous abortion was significantly related to maternal age, as shown in Tables III and IV, with a low risk for women under 35 years, but a much higher risk for older women. Table IV also shows that the abortion risk for older women with no previous abortion is high, but the rise in risk according to the number of previous spontaneous abortions is less than for younger women. There was no significant time trend during the study period in the overall risk of abortion. nor in the risk of abortion in any subgroup. In order to validate the information from DNPR, we attempted to review the discharge
IV
Risk of spontaneous Number of previous abortions
abortion.
according
to number
of previous
Age -C 35
consecutive
spontaneous
abortions
in relation
IO maternal
Age 2 35
”
risk (W)
n
risk (%)
1 2 3 4
16 806 a 18749 1908 291 78
9.7 14.9 23.8 43.0 53.8
1358 a 2 305 323 62 16
24.2 24.0 32.8 54.8 56.3
Overall
18178 a
10.2
1559 a
24.7 (22.6-26.9)
0
of the study
a A 6.6%sample of the study pregnancies. n. number of study pregnancies in subgroup. Figures in brackets : 95% confidence limits. Age c 35: x2 (trend) = 655; d/= 1; P < 0.0001. Age 3 35: x2 (trend) = 23.3: df= 1: P < 0.0001.
(9.2-10.1) (14.3-15.4) (21.9-25.8) (37.2-48.9) (42.2-65.2) (9.7-10.6)
(22.0-26.6) (22.3-25.X) (27.7-38.2) (41.7-67.5) (29.9-80.2)
age
34 TABLE V Validation study: Comparison of DNPR diagnoses with discharge summaries. Admissions after at least three previous spontaneous abortions (SA) Diagnosis according to discharge summaries
Diagnosis according to DNPR Birth
SA
Total
Birth SA Not pregnant
205 0 0
0 166 35
205 166 35
Total
205
201
406
DNPR: The Danish National Patient Register.
summaries on 479 spontaneous abortions and births after three or more previous spontaneous abortions. 406 discharge summaries (85%) were reviewed, as six hospitals did not provide copies of the discharge summaries. The main results of the validation study are shown in Table V. There was no misclassification of births, but 17% of admissions classified as spontaneous abortion in DNPR were in fact not pregnancy related. The source of this misclassification was the discharge diagnosis ‘habitual abortion’ which in some cases represented an actual abortion, while in others cases it represented admission of a non-pregnant woman with the purpose of investigating the cause of previous spontaneous abortions. The information in DNPR did not enable us to correct this error systematically. Discussion
In Denmark almost all births (99.3% in 1981) and all induced abortions take place in hospitals or clinics and are consequently registered in The Danish National Patient Register. Births not giving rise to hospital admission are not accounted for, but are probably very rare among women with previous spontaneous abortions. The bias induced by omitting these cases is therefore small. The number of spontaneous abortions not registered is unknown, but it is assumed that the large majority of clinically manifest abortions give rise to hospital admission, as all women in Denmark with clinical abortion are offered evacuation.
As the purpose of this study was to estimate the prognosis of the following pregnancy only clinical abortions were included, as subclinical abortions mainly are regarded as an infertility problem. The central registration in DNPR may be disposed to some misclassification, in spite of WHO’s clear criteria for the classification of diseases [lo]. Induced abortion is permitted on demand during the first 12 weeks of pregnancy in Denmark, but must be performed in a hospital by law. Because of this, misclassification between induced and spontaneous abortions is small. According to Susser [ll] the existence of high rates of induced abortion in a population may distort the rate of spontaneous abortion. In Denmark the induced abortion rate is around 27% of all pregnancies. Applying Susser’s model, which assumes the spontaneous abortion rate to be identical in women, who intend to seek abortion and those who do not, the ‘true spontaneous abortion rate’ is the number of spontaneous abortions divided by the total number of spontaneous abortions, the number of births taking place after 28 weeks and one half of the number of induced abortions. In our study the ‘corrected’ overall spontaneous abortion rate would be 9.3% compared to the crude 11.3%. The correction is mainly of interest for the overall spontaneous abortion rate, as women with habitual abortion rarely have an induced abortion. Abortions prior to 1977 were not recorded, making the estimated prognosis of a new pregnancy with respect to the number of previous abortions too pessimistic. The purpose of restricting the material to pregnancies terminated during 1980 to 1984 was to reduce information bias by allowing for the recording of at least 3 years of abortion/ birth experience. As there was no significant time trend in the risk of abortion conditional on the number of recorded previous abortions, the restriction seems to have been successful. As one birth or spontaneous abortion can give rise to several admissions, it was necessary to formulate a set of rules for the interpretation of the information about the individual discharges as described above. The elimination of admissions too close to a birth or spontaneous abortion can give rise to misclassification in some extreme cases.
35
The direction of this bias can not be determined, but the magnitude is probably small. In the validation study we found no misclassification from this source. The validation study demonstrated an overestimation by 17% of spontaneous abortions in study pregnancies after three or more previous spontaneous abortions, due to ambiguous use in DNPR of the diagnosis ‘habitual abortion’. In the validated cases the risk of abortion for women with three or more previous spontaneous abortions was 49.5% according to DNPR, in contrast to 44.7% according to the discharge summaries. On the other hand, this type of misclassification has also given rise to overestimations of the number of previous spontaneous abortions. Misclassification of previous spontaneous abortions has not been investigated, but since the diagnosis ‘habitual abortion’ depends on at least two prior spontaneous abortions, it is probably of minor magnitude. Overall, misclassification due to ambiguous use of the diagnosis ‘habitual abortion’ in DNPR has probably given rise to a somewhat elevated
TABLE
VI
Assessment Source mation
of bias due to missing
of possible
Births outside
SAs not tal h
misinfor-
hospital
or misclassified
information
Consequences for estimation of study pregnancies Negligible underestimate number of study births
admitted
to hospi-
Minor underestimate ber of study SAs
Induced abortions fied as spontaneous
misclassiabortions
Negligible underestimate number of study SAs
Abortions recorded
estimate of the risk of spontaneous abortion, conditional on the number of previous spontaneous abortions. Table VI is an overall assessment of the magnitude and direction of bias in the estimate of the spontaneous abortion risk, conditional on the number of previous consecutive spontaneous abortions. It is concluded that the total effect of incomplete information is probably a moderate overestimation of the conditional abortion risk. The estimates calculated should therefore be considered slightly pessimistic. The overall risk of spontaneous abortion in this study, 11.3’%, is lower than previously reported (see Table I), with the exception of Regan [12]. She found in a prospective study in Cambridge, England (1986), an overall spontaneous abortion rate of 10.3% and 5.6% for primigravidae. The low estimate in Regan’s study might, however, be due to patient selection. The low incidence of spontaneous abortion in our unselected population could be due to the use of effective contraceptives, and the opportunity for induced abortion on demand,
prior
of
of num-
of
to 1977 not
Habitual abortion admissions misclassified as SAs
Major overestimate ber of study SAs
Overall
Moderate overestimate number of study SAs
Consequences for estimated conditional SA risk ’
Consequences for estimation of prior pregnancies
of num-
of
Negligible underestimate number of prior births
of
Negligible error known direction
Minor underestimate of number of prior consecutive SAs
Minor error rection
Negligible underestimate of number of prior consecutive SAs
Negligible direction
Minor underestimate of number of prior consecutive SAs
Minor
Moderate overestimate of number of prior consecutive SAs
Minor or estimate
Minor over- or underestimate of number of prior SAs
Moderate
of
of unknown
error
un-
di-
of unknown
overestimate
moderate
overestimate
a Conditional SA risk: Risk of SA in a study pregnancy after a given number of prior consecutive SAs. b The event of interest is clinical abortion. Early subclinical pregnancy loss is not within the scope of the investigation. SA, spontaneous abortion.
over-
36
which means that most pregnancies not terminated by induced abortion were wanted and, thereby presumably less prone to complications. Our results are estimated from a large, unselected population obtained from a central register (DNPR). Previous reports of the outcome of a pregnancy following one or more spontaneous abortions are mainly based on small and often highly selected groups of women (see Table I). Most information in these groups is obtained by interview, and therefore prone to recall bias [5]. The association between the age of the mother and the spontaneous abortion rate has been discussed [3,4,6]. Our results show that the spontaneous abortion rate is steady up to the age of 35 years, but then increases remarkably, reaching 41% when the mother is over 40 years old. The increase in the spontaneous abortion rate in relation to previous spontaneous abortions can not be explained by the increase in maternal age alone. Poland et al. [4] found a significant increased risk of spontaneous abortion for women over 35 years of age, whereas Parazzini [13] found no influence of the maternal age. Our study confirms an increase in abortion rate by age, but the almost identical abortion rates after several abortions in young and old women indicate a risk factor, which is not age-related. Acknowledgment
This report was supported financially by The Danish Medical Research Council. References 1 Huisjes HJ. Spontaneous Abortion. Edingburgh: Churchill Livingstone, 1984.
2 Goldzieher JW, Benign0 BB. The treatment of threatened and recurrent abortion: a critical review. Am J Obstet Gynecol 1958;75:1202-1214. 3 Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet 1964;16:1-25. 4 Poland BJ, Miller JR, Jones DC, Trimble BK. Reproductive counseling in patients who have had a spontaneous abortion. Am J Obstet Gynecol 1977;127:685-691. 5 Naylor AF, Warburton D. Sequential analysis of spontaneous abortion. II. Collaborative study data show that gravidity determines a very substantial rise in risk. Fertil Steril 1979;31:282-286. 6 Leridon H. Facts and artifacts in the study of intra-uterine mortality: a reconsideration from pregnancy histories. Population Studies 1976;30:319-335. 7 Kline J, Shrout PE, Stein ZA, Susser M, Weiss M. II. An epidemiological study of the role of gravidity in spontaneous abortion. Early Hum Dev 1978;1:345-356. 8 National Board of Health. Klassifikation af sygdomme, 8.revision 1965. Systematisk fortegnelse. Copenhagen, 1982. 9 Armitage P. Statistical methods in medical research. London: Blackwell Scientific Publications, 1974. 10 National Board of Health. Evaluering af Landspatientregisteret. En pilotundersegelse. Sygehusstatistik 1984;11:19. 11 Susser E. Spontaneous abortion and induced abortion: an adjustment for the presence of induced abortion when estimating the rate of spontaneous abortion from cross-sectional studies. Am J Epidemiol. 1983;117:305-308. 12 Regan L. A prospective study of spontaneous abortion. Early pregnancy loss: mechanisms and treatment. In: Beard RW, Sharp F (eds). Proceedings of the 18th study group of the Royal College of Obstetricians and Gynaecologists. 1988;23-37. 13 Parazzini F, Acaia B, Ricciardiello 0, Fedele L, Liati P, Candiani GB. Short-term reproductive prognosis when no cause can be found for recurrent miscarriage. Br J Obstet Gynaecol 1988;95:654-658. 14 Malpas P. A study of abortion sequences. J Obstet Gynaecol Br Emp 1938;45:932-949.