Women who deliver preterm at risk of premature death

Preterm and early-term delivery are independently associated with the risk of premature mortality from several major causes, and these associations decline over time but persist for up to 40 years later, suggest the results of a national cohort and co-sibling study in Sweden.

“Women who deliver prematurely need long-term clinical follow-up for detection and treatment of chronic disorders associated with early mortality,” the researchers said.

All 2,189,477 women with a singleton delivery from 1973 to 2015 were included in this study. The researchers identified all-cause and cause-specific mortality up to 2016 from nationwide death records. They used Cox regression to estimate hazard ratios (HRs) while adjusting for confounders and performed co-sibling analyses to examine the potential influence of unmeasured shared familial factors.

Of the women, 76,535 (3.5 percent) died (median age at death, 57.6 years) over 50.7 million person-years of follow-up. The adjusted HR in the first 10 years after delivery was 1.73 (95 percent confidence interval [CI], 1.61–1.87) for all-cause mortality associated with preterm delivery (<37 weeks). [BMJ 2020;370:m2533]

When further stratified, the HRs were 2.20 (95 percent CI, 1.63–2.96) for extremely preterm delivery (22–27 weeks), 2.28 (95 percent CI, 2.01–2.58) for very preterm delivery (28–33 weeks), 1.52 (95 percent CI, 1.39–1.67) for late preterm delivery (34–36 weeks), and 1.19 (95 percent CI, 1.12–1.27) for early term delivery (37–38 weeks) compared with full term delivery (39–41 weeks).

Such risks declined but remained significantly elevated after longer follow-up times. The adjusted HRs for mortality were 1.45 (95 percent CI, 1.37–1.53) for preterm vs full-term births 10–19 years after delivery and 1.37 (95 percent CI, 1.33–1.41) in 20–44 years after delivery.

“These findings did not seem to be attributable to shared genetic or environmental factors within families,” the researchers said. “Several causes were identified, including cardiovascular and respiratory disorders, diabetes, and cancer.”

Furthermore, these findings support those of earlier studies exploring the birth weight of infants in relation to future health risks in the mother. Other studies also found increased cardiovascular and diabetes-related mortality in women who delivered an infant with a low birth weight. [Cancer Causes Control 2015;26:1593-1601; Ann Epidemiol 2009;19:112-117; Am J Epidemiol 2007;166:160-169; Lancet 2000;356:2066-2067; Lancet 2001;357:2002-2006; Epidemiology 2005;16:563-569; J Epidemiol Community Health 2011;65:775-779]

“We found several major causes of death associated with preterm delivery, including cardiovascular and respiratory disorders, diabetes, cancer, and other causes,” the researchers said. “These findings are similar to previously reported cause-specific mortality in the offspring of preterm birth.” [Lancet Child Adolesc Health 2019;3:408-417; JAMA 2011;306:1233-1240; Epidemiology 2013;24:270-276]

Of note, common genetic factors were also thought to influence preterm delivery and future health outcomes, but co-sibling analyses suggested that the current findings were independent of shared genetic or early life environmental factors within families. [Semin Reprod Med 2007;25:40-51]

“Instead, individual specific processes involved with preterm delivery might contribute directly to subsequent development of chronic disorders and early mortality in women,” the researchers posited. “The mechanisms are not established but could involve common inflammatory pathways.”