Preterm delivery tied to raised mortality risk

Preterm delivery (<37 weeks) was an independent risk factor for premature mortality compared with full-term delivery (39–41 weeks), with risks persisting for up to 40 years later, a study suggests.

Despite evidence reporting the health risks of preterm delivery, little is known about its associated mortality risks. [J Womens Health (Larchmt) 2019;28:677-685; J Am Heart Assoc 2018;7:e007809; J Am Coll Cardiol 2020;76:57-67] “A better understanding of these outcomes is [thus] needed to identify women at high risk and guide their long-term clinical care,” said the researchers.

Data of >2 million women with a singleton delivery from the Swedish Medical Birth Register were included in the analysis. Median ages at first delivery and end of follow-up were 27 and 50 years, respectively. In 50.7 million person-years of follow-up, 3.5 percent (n=76,535) of women had died (median age at death 57.6 years). [BMJ 2020;370:m2533]

All-cause mortality risk was higher in women who delivered preterm vs those who delivered full-term at <10, 10–19 and 20–44 years after delivery (adjusted hazard ratios [adjHRs], 1.73, 1.45, and 1.37, respectively).

When data for <10 years after delivery were stratified, elevated mortality risks were tied to extremely preterm (22–27 weeks; adjHR, 2.20), very preterm (28–33 weeks; adjHR, 2.28), late preterm (34–36 weeks; adjHR, 1.52), and early term deliveries (37–38 weeks; adjHR, 1.19) vs full-term delivery.

“[These imply that] length of pregnancy in women was inversely associated with their long-term mortality risk after adjusting for many other risk factors … These findings suggest that all women who deliver preterm, and not only subgroups with other major complications, have raised mortality risks,” said the researchers.

Co-sibling analyses

In the co-sibling analyses, the adjusted HRs for mortality for preterm vs full-term delivery were 1.68, 1.46, and 1.37 at <10, 10–19, and 20–44 years after delivery, respectively. “These findings suggested that the associations seen in the primary analyses were not attributable to shared genetic or early life environmental factors in families,” the researchers explained.

Early mortality risk in women may thus be attributed to other factors such as pro-inflammatory pathways, cardiometabolic disorders, and vitamin D deficiency. [J Leukoc Biol 2016;99:67-78; J Allergy Clin Immunol 2016;138:16-27; J Obstet Gynaecol Res 2017;43:247-256; J Steroid Biochem Mol Biol 2015;148:256-260] “Further experimental and clinical studies are needed to identify the relevant mechanisms, which might disclose new targets for prevention,” said the researchers.

Improving risk stratification

“[Taken together, our findings suggest that] premature delivery should now be recognized as a risk factor for early mortality in women,” said the researchers. Medical records should reflect reproductive history covering preterm delivery and other pregnancy complications, they added.

“Women with a history of preterm delivery need long-term follow-up for recommended screenings to facilitate detection and treatment of chronic disorders associated with early mortality … Better access to high-quality preconception and prenatal care should also be a public health priority to help reduce preterm delivery,” they continued.

Despite the large, diverse population and the long follow-up, data on spontaneous or medically indicated preterm delivery was only available from 1990 which, as per the researchers, “allowed exploratory analyses only in a large subcohort”. Also, confounding by maternal smoking, body mass index, or other factors remain despite controlling for several maternal factors and shared familial exposures. The results may also not be generalizable to other populations as the study was limited to Sweden, they added.

It is thus imperative to conduct studies in other diverse regions to evaluate responses in other ethnic and racial subsets, the researchers noted. “Longer follow-up to older ages will be needed in this or other large cohorts when such data become available … More complete assessment of the underlying causes of preterm delivery would be useful in future studies to further improve risk stratification.”