The present study sample included 20 846 primiparous women selected from a study population of 51 960 women. To our knowledge, no study of this magnitude has previously been conducted to explore the effect of prior abortions on pre-eclampsia risk.
In accordance with the long established fact that a previous birth is protective of pre-eclampsia in later pregnancies, the results from the present study show that this is true also for previous induced abortions in primiparous women. We found a >50% reduced risk of pre-eclampsia in primiparous women with two or more induced abortions as compared with all other subgroups, including women with one induced abortion. When compared with all women with singleton pregnancies in the study population (n = 47 304), the risk of pre-eclampsia in primiparous women with two prior induced abortions was similar to the pre-eclampsia risk in women with one prior birth (2.1% vs 2.5%). The pre-eclampsia risk in primiparous women was 5.4%.
The risk of pre-eclampsia in women with two or more induced abortions tended to be lower in both same paternity and new paternity pregnancies, as compared with primigravid women (1.4% and 2.5% vs 5.5%, ). Stratified analyses to further explore the impact of changed paternity and gestational length at the time of the abortion on the pre-eclampsia risk were restricted by small numbers.
The strength of the present study, in addition to the large study sample, is the distinction between induced and spontaneous abortions and the ability to adjust for several confounders, including time interval since the last abortion and change in paternity. No previous study has corrected for pregnancy interval. The present study used a prospective cohort design where information on previous pregnancies, smoking habits and other exposures were collected before pre-eclampsia had developed clinically.
Misclassification due to under- or over-reporting of prior abortions by the women in the study may represent a potential weakness. However, the proportion of women in the study reporting one or more previous spontaneous abortions (15.1%) is similar to the proportion of women registered in the MBRN (15.0%) with previous spontaneous abortion(s). Nevertheless, the information on abortions both in MoBa and in the MBRN may be subject to underreporting leading to an underestimation of the effect of abortions on the pre-eclampsia risk.
Twice as many women in the induced abortion group were daily smokers as compared with primigravid women or women with previous spontaneous abortions. Smoking is associated with a reduced risk of pre-eclampsia,15
thus residual confounding due to lack of control for the amount of cigarettes smoked by women with induced abortions could be argued to explain the reduced risk in this group. Additional analyses adjusting for the number of cigarettes smoked did, however, not change the estimates.
For information on change in paternity between the last abortion and the index pregnancy, a proxy variable based on the duration of cohabitation was used. This represents an inaccuracy that may potentially influence the results. In , we aimed to assess whether the reduced risk after two induced abortions was seen both for women with the same partner and with a new partner. Random misclassification of paternity would tend to reduce any differences between these two groups.
Some previous studies on the effect of abortions on later pre-eclampsia risk have been published. Using a dataset including 2947 healthy women from a clinical trial of aspirin, Sibai et al.4
reported that primiparous women with no earlier abortions had a pre-eclampsia risk of 5.7%, while women with one prior abortion had a risk of 4.7% and women with two earlier abortions had a risk of 1.8%. They did not differentiate between spontaneous and induced abortions. In a similar trial, the Calcium for Preeclampsia Prevention (CPEP) trial, Sibai et al.5
studied 4314 primiparous women and reported that the risk of pre-eclampsia was 8.0%, 6.5% and 5.7% for women with none, one and two earlier abortions, although these differences were not statistically significant. Again, no differentiation between induced and spontaneous abortions was made. Saftlas et al.6
also used the CPEP data set, restricting the sample to 3242 primigravidas and 822 women with one previous abortion, and reported that a substantial pre-eclampsia risk reduction (from 8.0% to 4.3%) occurred for the subgroup of women with one abortion (without reporting effects of induced vs spontaneous abortions) and the same father, whereas the risk was not reduced if a change of partner had taken place. The mean maternal age in the CPEP study was 22 years, limiting the possibility of studying long pregnancy intervals. Xiong et al.7
used a large Canadian data set based on hospital records and found that the risk of pre-eclampsia was 2.9% in primigravid women and 2.6% in primiparous women with a previous abortion, but could not differentiate between induced and spontaneous abortions. Thus, all these studies suggest a certain reduction in risk if a primiparous woman has experienced any abortion.
Eras et al.
using records from obstetric practices for 2739 births, reported a significant reduction in pre-eclampsia risk both for women who had experienced one spontaneous abortion and one induced abortion as compared with primigravidas. Beck11
reviewed case records of 220 women who had had an abortion before the first term pregnancy. He found that the incidence of pre-eclampsia was significantly lower when there had been a previous induced abortion as compared with no previous abortion or previous spontaneous abortion. Also, the interval between the first and second pregnancy was longer in women having had a previous induced abortion as compared with a previous spontaneous abortion, but there were no difference in the mean time interval between normal pregnancies and pregnancies complicated by pre-eclampsia. In a sample of 9771 women pregnant for the first or second time, Seidman and colleagues10
found a protective effect of a prior induced abortion after adjustment for maternal age, social class, ethnic origin and smoking, but no protective effect of a previous spontaneous abortion. Campbell et al.16
found that the incidence of pre-eclampsia after early abortion (<13 weeks), either spontaneous or induced, was similar to the population incidence in a first pregnancy. Thus, our results are consistent with the findings of Beck and with the findings of Seidman and colleagues, but not with Campbell's observation.
The mechanisms behind the parity effect are not understood. A relatively new observation is that the inter-pregnancy interval may be a major determinant. If the time since the previous birth is 11 years of more, the risk of pre-eclampsia in second births appears to be as high as in a first birth.1–3
In our study, the mean time interval from an induced abortion to birth was about 6 years, which may dilute a protective effect. Women with prior induced abortions had a much longer time interval between the abortion and the subsequent delivery than women with prior spontaneous abortions. Nevertheless, adjustment for the time interval between the abortion and the subsequent birth did not change the pre-eclampsia risk among women with same paternity pregnancies, nor in new paternity pregnancies. Thus, the increased risk of pre-eclampsia with increasing interval between the first and second birth demonstrated in a previous study1
could not be demonstrated for abortions and subsequent pre-eclampsia risk in the present study. The lack of association may perhaps be explained by differences in gestational age, however small numbers restricted us from further analyses.
Recent studies have reported that both maternal and paternal genes influence the risk of pre-eclampsia. Mothers and fathers themselves born from pre-eclamptic pregnancies contribute to an increased risk in the next generation.17–19
Although there was a tendency that women with changed paternity were slightly less protected by two or more previous induced abortions, and slightly more protected by two or more previous spontaneous abortions as compared with women with no change in paternity, these findings were not significant and caution should be taken to draw conclusions. Thus the impact of changed paternity on the pre-eclampsia risk remains unresolved. However, it seems likely that a change in paternity may increase or decrease the risk of pre-eclampsia, depending on the paternal genes transmitted to the foetus and their interaction with maternal genes. This is opposed to the immune based primipaternity hypothesis suggesting the first pregnancy of any father will increase pre-eclampsia risk.20
We have not been able to control for the genetic predisposition to pre-eclampsia in the parenting men and women in this study.
Although genetic factors inevitably are important in the development of pre-eclampsia, they are unlikely to explain the reduced risk in second and later pregnancies. We speculate whether any pregnancy to a woman induces a ‘memory’ which reduces the risk of pre-eclampsia in a subsequent pregnancy, regardless of the parental genetic contributions which may also alter the risk between pregnancies. This ‘memory’ may be hypothesized to decrease with increasing time since the pregnancy, as reflected by the increased risk observed with long interpregnancy intervals.1
An induced abortion can in most instances be assumed to be a normal pregnancy in contrast to a pregnancy that ends in a spontaneous abortion. The underlying pathology behind a spontaneous abortion may in itself predispose to pre-eclampsia.21
We found that women with spontaneous abortions more often had been treated for infertility. Basso et al.22
have suggested that subfecundity and pre-eclampsia may share the same etiology. Thus, the protective effect of a spontaneous abortion on pre-eclampsia risk in a subsequent pregnancy may be overshadowed by risk-increasing factors, and should be studied further.
In summary, we have found a significant protective effect of having two or more induced abortions prior to the first birth on the risk of pre-eclampsia. The protective effect of two prior induced abortions is similar to the protective effect of one prior birth. The time interval between the abortion and the subsequent birth did not influence the results. The impact of changed paternity remains unresolved. We speculate that normal pregnancies that are interrupted in early pregnancy may induce immunological changes that reduce the risk of pre-eclampsia in a subsequent pregnancy, regardless of partner change.