Preterm delivery ups stroke risk in women

Women with shorter pregnancy duration are likely to develop haemorrhagic or ischaemic stroke in the future, with the risk remaining elevated at least 40 years later, a large study has found.

In light of the findings, preterm delivery should be recognized by clinicians and patients as an important risk factor for stroke and other cardiovascular disease across the life course, according to the investigators. As such, “cardiovascular risk assessment in women should routinely include reproductive history that covers preterm delivery and other adverse pregnancy outcomes.”

For women with a history of preterm delivery, the investigators called for early preventive interventions and long-term clinical follow-up to manage other modifiable risk factors for stroke, such as obesity, hypertension, diabetes, hyperlipidaemia, smoking, and physical inactivity. “Better access to high-quality preconception and prenatal care is also critically needed to help reduce preterm delivery.”

The study comprised a cohort of 2,188,043 women with a singleton delivery, among whom 36,372 (1.7 percent) were diagnosed with stroke over 48.0 million person-years of follow-up. Preterm birth (gestational age <37 weeks) was associated with a 61-percent increase in the risk of any stroke (adjusted hazard ratio [aHR], 1.61, 95 percent confidence interval [CI], 1.45–1.79; p<0.001) in the 10 years after delivery. [Circulation 2021;143:2032-2044]

Notably, the risk increase was observed across all preterm birth categories. Using full term (39–41 weeks) as reference, extremely preterm (22–27 weeks) conferred the highest risk of stroke (aHR, 2.81, 95 percent CI, 2.02–3.91). This was followed by very preterm (28–33 weeks; aHR, 2.07, 95 percent CI, 1.74–2.46), late preterm (34–36 weeks; aHR, 1.38, 95 percent CI, 1.21–1.57), and early term (37–38 weeks; aHR, 1.15, 95 percent CI, 1.06–1.24).

Stroke risks persisted at 10 to 19 years after delivery (preterm vs full-term: aHR, 1.61, 95 percent CI, 1.50–1.74) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35, 95 percent CI, 1.28–1.44) and 30 to 43 years (aHR, 1.35, 95 percent CI, 1.27–1.42).

Preterm delivery was a risk factor for both ischaemic (aHR, 1.54, 95 percent CI, 1.47–1.61) haemorrhagic (aHR, 1.31, 95 percent CI, 1.25–1.38) stroke across the entire follow-up period (up to 43 years). Furthermore, the risks were pronounced after either spontaneous or medically indicated preterm delivery, with recurrent preterm delivery conveying further risk increases.

“Findings in the present study were largely independent of covariates and unmeasured shared genetic or environmental factors in families… [and the] overall risk estimates for stroke were consistent with those from previous smaller studies,” the investigators noted. [BMC Pregnancy Childbirth 2015;15:144; Ann Epidemiol 2010;20:604-609; Circulation 2017;135:578-589; Stroke 2011;42:716-721; J Am Heart Assoc 2018;7:e007809]

They pointed out that the associations observed in the study indicated that “individual-specific processes involved in preterm delivery may have direct effects on future development of stroke.”

Common causes of preterm delivery such as pre-eclampsia and other hypertensive disorders of pregnancy contribute to lifelong higher risks of hypertension, which in turn is a major risk factor for both haemorrhagic and ischaemic stroke, and stroke mortality. [Lancet 2016;388:761-775; BMJ 2003;326:845; Obstet Gynecol 2016;128:238-244]  

“However, our findings suggested that hypertension only partially mediated associations between preterm delivery and either haemorrhagic or ischaemic stroke. Other mechanisms may potentially involve inflammatory pathways that have been linked to preterm delivery and endothelial dysfunction,” the investigators said.

“Further elucidation of the underlying mechanisms is needed and may reveal new targets for intervention to prevent both preterm delivery and subsequent stroke,” they added.