1 Department of Social Medicine, University of Bristol, Bristol BS8 2PR, 2 London School of Hygiene and Tropical Medicine, London and 3 Leukaemia Research Fund, University of Leeds, Leeds, UK
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Abstract |
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Key words: epidemiology/fetal death/infertility/reproductive history
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Introduction |
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The objective of this study was to examine the effects on fetal death (defined as stillbirth or miscarriage at any gestational age) of reproductive history and other maternal risk factors, and to explore the relationships between them. Analysis of the effect of reproductive history on future pregnancy outcome is known to be prone to bias (Olsen, 1994; Weinberg et al., 1994
) and the methodological approach adopted here attempts to address these potential problems.
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Materials and methods |
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Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. P values were based on appropriate likelihood ratio tests for trend or interaction unless otherwise specified.
Preliminary analyses concentrated on all pregnancies combined, exploring the effects on fetal death of year of pregnancy outcome, maternal age, height, smoking and fertility. It has been suggested (Hakim et al., 1995) that the adverse effect of infertility may be greater in older women and an appropriate interaction term was also included to investigate this potential synergism. Robust standard errors were calculated (Huber, 1967
) to allow for the correlation between women's successive pregnancy outcomes.
To allow for the problem of women with a history of fetal death being over-represented, additional separate analyses were carried out for each of pregnancy orders 1, 2 and 3 (there were insufficient numbers to continue this approach for higher order pregnancies). These analyses considered those factors found to be significantly associated with pregnancy outcome in the analysis of all pregnancies combined. For pregnancy orders 2 and 3, additional terms were included to assess the impact of previous pregnancy outcomes. In second pregnancies, previous history was included as the outcome of the first. For third pregnancies, previous history was included as: (i) two terms representing the outcomes of each previous pregnancy; and (ii) total number of previous fetal deaths.
Analyses were carried out using data from women who had only ever had singleton live births or fetal deaths. The majority of excluded women had induced abortions. To assess the impact of these exclusions, analyses were repeated using data from all women in three ways: (i) using data from all women but dropping individual pregnancies with an outcome other than a live birth or fetal death; (ii) using data from all women, with induced abortions treated as live births and dropping pregnancies with other outcomes; (iii) the analysis of previous pregnancy outcomes was repeated with outcomes other than a fetal death or live birth included as a risk factor for subsequent fetal losses. In all analyses, multiple births were included as live births. Because some women might not have completed their families by the time of the survey, all analyses were repeated for those aged 40 years or over.
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Results |
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The women were aged between 30 and 64 years with 1686 (55%) aged 40 years or over (Table I). Two thousand and three (66%) were lifelong non-smokers, 674 (22%) ex-smokers, and 376 (12%) current smokers. The majority (80%) reported no difficulties in conceiving any pregnancies (fertility type A). However, 276 (9%) were classified as fertility type B, 144 (5%) type C, and 182 (6%) unknown. The total number of live births ranged from 0 to 6, with 1701 women (56%) reporting two. The total number of fetal deaths ranged from 0 to 8 with 2310 women (76%) reporting none. Sixty women (2%) reported only having pregnancies ending in a fetal death.
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When women with other pregnancy outcomes were included, the results of the analyses were very similar (data not shown). There was some evidence of a raised risk of fetal death following one of these other outcomes (mostly induced abortions) but the numbers involved were small. Restricting attention to women over 40 years revealed that, although the older women had more live births in total, the proportion with at least one fetal death was almost identical to that in younger women and the results of the analyses were very similar (data not shown).
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Discussion |
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The pattern of increasing risk of fetal death following a previous loss has been widely reported elsewhere (Leridon, 1976; Roman et al., 1978
; Risch et al., 1988
; Kline et al., 1989
; Regan et al., 1989
; Coste et al., 1991
; Parazzini et al., 1997
). In the current analysis a similar association is seen, particularly in third pregnancies with a suggestion that it is the most recent event (i.e. the outcome of the second pregnancy) which has the greatest impact. However, it is difficult to attach much weight to this without similar evidence from higher order pregnancies. In these limited data it may be more informative to consider the number of previous fetal deaths. The increase in OR associated with one and two previous losses suggests that the effect may be cumulative and the magnitude of this change is consistent with a multiplicative effect.
These data came from a retrospective cohort study and the possibility of recall bias should be considered. It is possible, for example, that the absence of an association between fetal death and smoking status might be explained by poor recall or under-reporting of past smoking habits by women who had fetal deaths. A particular problem in this type of study is the self-reporting of pregnancy outcomes. If women with previous fetal losses were more likely to recognize a subsequent early loss, the risk of fetal death following a previous loss would be exaggerated. Similarly, women may have been more likely to recall more recent fetal losses which might, in part, explain the apparent trend of increasing fetal death with increasing year of pregnancy outcome.
There are also potential problems with the fertility measure used here, as women with a successful pregnancy history may be less likely to perceive any retrospective difficulty in conception, leading to an overestimate of the harmful effect of reduced fertility. In addition, assigning the same fertility type to all of a woman's pregnancies is not ideal as fecundity is known to decrease with age (Schwartz and Mayaux, 1982), making it potentially unrealistic to assume that the same difficulty applies equally to all pregnancies. Moreover, it is not possible to establish in these data whether the observed association suggests that subfertility leads to an increased risk of fetal death or vice versa.
Bias may also be introduced by omitting women with pregnancies not ending in a live birth or fetal death. However including these women, and in particular their induced abortions, made no perceptible difference to the results. The additional finding of a possible increase in risk of fetal death following an induced abortion is interesting, particularly in light of speculation that there may be damage caused to the cervix (Molin, 1993), but it is not possible to draw any conclusions from these restricted data.
There is still much to learn about factors that affect pregnancy outcome and the way in which they interact. In addition to recognised risk factors for fetal death, it is important to assess the impact of past reproductive experience. These data support the notion that having a previous fetal death may increase the risk of a subsequent loss. Analysis of the number of previous losses suggests that this increase in risk may be cumulative and possibly multiplicative in effect. There is also evidence of an association between subfertility and risk of fetal death, regardless of pregnancy order and previous pregnancy outcomes, and this is particularly marked in the pregnancies of older women.
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Notes |
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References |
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Submitted on January 19, 1999; accepted on August 5, 1999.