Preterm delivery is a maternal risk factor of CVD
Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women
Background
In the United States ~10% of the deliveries are preterm [1]. It has been hypothesized that pregnancy complications, including preterm delivery, as well as HDP (preeclampsia and gestational hypertension), provide a warning sign of future cardiovascular disease (CVD) risk, that could be useful in identifying high-risk women early in adult life before the appearance of clinical risk factors [2-4]. Prior literature describes a 2-fold increased risk of future CVD events for women who delivered preterm, however, in these studies was not corrected for CVD risk factors and prepregnancy lifestyle such as smoking, physical activity, diet, BMI and family history of CVD [5-7].
Therefore, this study (Nurses’ Health Study II), including 70 182 US registered nurses between 25 and 42 years of age at baseline, evaluated the association between preterm delivery and CVD (myocardial infarction [MI] or stroke) and to what extent this is related to postpartum development of traditional CVD risk factors (chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus [T2DM] and BMI). Preterm delivery was categorized as term (≥37 weeks), moderate preterm (≥32 and <37 weeks) or very preterm (<32 weeks). Follow up was until 50 years of age and started in 1989.
Main results
- First pregnancy: 2.1% very preterm, 6.7% moderately preterm and 91.2% at term.
- Women who delivered moderately or very preterm were slightly more like to have a BMI ≥30 kg/m2, pregnancy hypertension and hypercholesterolemia and a family history of CVD. Furthermore, women who delivered very preterm were more likely to be current smokers, experience a stillbirth in first pregnancy and have higher final parity.
- 949 CVD events occurred; 584 definite and 365 probable.
- After adjustment for confounding lifestyle and CVD risk factors, women who had a preterm first birth had an increased rate of CVD (HR 1.42, 95% CI 1.16-1.72).
- When split into 2 categories, the HRs for moderate preterm and very preterm were 1.22 (95% CI 0.96-1.54) and 2.01 (95% CI 1.47-2.75), respectively (trend P<0.0001).
- When analysing stroke and MI separately, results were slightly stronger for MI.
- Increased rate of CVD was present in very preterm live birth (HR 1.98, 95% CI 1.27-3.08) as well as very preterm stillbirth (HR 2.07, 95% CI 1.35-3.18).
- Increased rate of CVD was present in normotensive preterm first pregnancy (HR 1.35, 95% CI 1.06-1.72) but higher in those with both preterm delivery and HDP in first pregnancy (HR 1.66, 95% CI 1.02-2.70).
- Rate was non-significantly higher in normotensive moderate preterm (HR 1.12, 95% CI 0.83-1.52) than in normotensive very preterm individuals (HR 2.01, 95% CI 1.38-2.93).
- Women with a preterm first birth and at least 1 later preterm birth had the largest fully adjusted HR (1.65, 95% CI 1.20-2.28).
- Women with only 1 child (either preterm or term) had an increased rate of CVD compared to women with at least 2 children at term.
- Increased CVD risk was applicable to both women with preterm delivery in the first pregnancy and later preterm deliveries.
- Regarding prepregnancy lifestyle, only chronic hypertension before first pregnancy appeared to be a confounder; HR moderate preterm vs. term were 0.21 (95% CI 0.03-1.52) for with and 1.30 (95% CI 1.02-1.64) for without prepregnancy chronic hypertension and HR very preterm with term were 0.57 (95% CI 0.08-4.14) for with and 2.12 (95% CI 1.54-2.92) for without prepregnancy chronic hypertension.
- 12.8% (95% CI 7.1-21.9) of the association between preterm delivery and CVD was related to postpartum development of chronic hypertension, T2DM, hypercholesterolemia or changes in BMI and was attenuated (5.9%, 95% CI 8.7-27.3) when breastfeeding was also included.
Conclusion
Women who deliver a preterm infant have an increased risk of future CVD events, which was higher for those who deliver before week 32. This risk is only partially explained by the subsequent development of traditional CVD risk factors, but this suggests that modification of these risk factors in these women may decrease the risk of CVD development. As a large part could not be explained by risk factors, additional pathways that link preterm delivery and CVD need to be further explored. Moreover, preterm delivery may be a valuable additional CVD risk marker in screening.
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