Spontaneous loss of early pregnancy and risk of ischaemic heart disease in later life: retrospective cohort study

We recently showed that complications in late pregnancy are associated with an increased risk of maternal ischaemic heart disease (IHD) in later life.¹ We hypothesised that this may reflect common determinants, such as thrombophilic genetic defects and anticardiolipin antibodies. Spontaneous losses of pregnancy are also associated with inherited and acquired thrombophilias in the mother.² We examined whether spontaneous losses of early pregnancy are associated with maternal risk of IHD.

Participants, methods, and results

We used routine national maternity data (SMR2) to identify all 129 290 eligible women who delivered their first liveborn infant in Scotland during 1981-5. The exclusion and inclusion criteria, definitions, and demographic characteristics were as previously described.¹ We used national death (GRO) and discharge (SMR1) data to determine the risk of death or hospital admission due to IHD during 1981-99. The cumulative probabilities of survival free from IHD events were assessed with Cox's proportional hazards models with age as the time scale (Stata version 7.0, StataCorp, College Station, TX,USA).

A history of any spontaneous loss of early pregnancy before the first live birth was associated with an increased risk of IHD (table). The association was independent of maternal age at the time of first birth, height, socioeconomic deprivation, essential hypertension, and complications during the first pregnancy. The magnitude of the risk increased with the number of previous losses. By contrast, there was no association between therapeutic abortion and subsequent risk of IHD (adjusted hazard ratio 0.93, 95% confidence interval 0.59 to 1.46). Only 0.1% (162) of women had had a hernia repair, and there was no significant association with spontaneous early pregnancy loss (0.93, 0.55 to 1.59), suggesting that there was no bias due to selective migration. We did not have data on the smoking status of women in the 1981-5 cohort. However, we had data on 181 636 women who had a first livebirth from 1992 to 1998, inclusive. The proportion of women who were current smokers at the first attendance for prenatal care was only marginally higher among women with a history of spontaneous loss of early pregnancy (28.4%) than among those with no such history (26.8%).

Comment

To our knowledge, this is the first study to show a specific association between spontaneous abortion and maternal risk of IHD. Our findings may explain the results of previous studies that have found an association between the total number of pregnancies and maternal risk of IHD as women who suffer recurrent losses of early pregnancy must have more pregnancies to achieve their target family size.³ However, it is unlikely that the association between spontaneous abortion and maternal IHD is simply an effect of parity as there was no association with therapeutic abortion.

The strengths of our study are that prospective data collection precluded bias and, in contrast with a case-control study, we were able to include women who subsequently died. However, further studies are required to corroborate our findings and to confirm that the association is independent of smoking and other confounding factors, such as maternal disease (for example, diabetes and polycystic ovarian syndrome).

Several studies have shown associations between acquired and inherited thrombophilias and both spontaneous loss of early pregnancy ² and IHD.⁴,⁵ Implantation of the embryo and development of the placenta involve complex adaptations of the mother's cardiovascular and microvascular systems. We hypothesise that occult cardiovascular, microvascular, or haemostatic dysfunction result in pregnancy complications during reproductive years and in overt cardiovascular disease in later life. A woman's reproductive history may, therefore, inform future cardiovascular risk.

Table.

Maternal ischaemic heart disease events and number of previous spontaneous losses of early pregnancy losses. Figures are hazard ratios (95% confidence interval)^*

	No of losses of early pregnancy
	0†(n=117 538)	1-2(n=11 371)	⩾3(n=381)	⩾1(n=11 752)
No (%) of events	261 (0.2)	48 (0.4)	4 (1.0)	52 (0.4)
Crude	1.0	1.44 (1.06 to 1.97), P=0.02	2.34 (0.87 to 6.32), P=0.09	1.49 (1.10 to 2.01), P=0.009
Adjusted for case mix‡	1.0	1.47 (1.08 to 2.00), P=0.02	2.32 (0.86 to 6.27), P=0.10	1.51 (1.12 to 2.04), P=0.007
Adjusted for case mix‡ and obstetric complications§	1.0	1.48 (1.09 to 2.02), P=0.01	2.35 (0.87 to 6.36), P=0.09	1.52 (1.13 to 2.06), P=0.006

^*All covariates in multivariate models were significantly associated with ischaemic heart disease. Proportional hazard assumption tested with Stata “stphtest” command with Schoenfeld residuals. There was no evidence for violation of assumption in any model (all P>0.5). 

^†Reference category. 

^‡Age, height, deprivation, and essential hypertension in first pregnancy. 

^§Lowest fifth of birthweight distribution, preterm delivery, pre-eclampsia.