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Seasonality was associated with a very small proportion of all extremely preterm births, according to a nationwide study in Denmark.

Of 2,009 extremely preterm births, the cumulative incidence of these births was lowest in winter (0.16%, 95% CI 0.14%-0.17%) and highest in autumn (0.20%, 95% CI 0.18%-0.21%), reported Anders Hviid, DMSc, of Statens Serum Institut in Denmark, and colleagues.

Cumulative incidence was next highest in summer (0.18%, 95% CI 0.17%-0.20%) and third highest in spring (0.17%, 95% CI 0.16%-0.19%), they noted in .

Compared with winter, the adjusted hazard ratios for the risk of extremely preterm birth were 1.11 (95% CI 0.97-1.26) for spring, 1.15 (95% CI 1.02-1.31) for summer, and 1.25 (95% CI 1.10-1.42) for autumn.

"Our results were, to some extent, consistent with both higher temperatures during months of gestation and lower temperatures during months of pregnancy onset, which may be associated with increases in the risk of extremely preterm birth," Hviid and team wrote, noting that this was in line with a that found heat and humidity increased risk of preterm birth.

The number of extremely preterm births associated with the increased risk in spring, summer, and autumn was 56.1, or 2.8% of all extremely preterm births in the study, the authors said.

Season of pregnancy onset was not linked to risk of extremely preterm birth in spring (aHR 0.98, 95% CI 0.95-1.01) or summer (aHR 1.00, 95% CI 0.96-1.03) versus winter, though there was a slight increase in risk in autumn (aHR 1.05, 95% CI 1.02-1.09) compared with winter.

Overall, when all preterm births -- including extremely preterm births, very preterm births, and moderately preterm births -- were combined, the rate was not associated with seasonality, they said.

During the early months of the COVID-19 lockdown, Denmark saw a . Lockdown behaviors such as focus on hygiene, working from home, social distancing, changes in physical activity patterns, and reductions in climate exposure may have contributed, Hviid and colleagues noted. Seasonality also affects these behaviors to a "similar, although less extreme" extent, they pointed out.

However, "before seasonality can be considered a definitive risk factor for preterm birth (extremely preterm or otherwise), several important caveats must be considered," wrote David Nelson, MD, and Catherine Y. Spong, MD, of the University of Texas Southwestern Medical Center in Dallas, in a .

They noted significant differences between the characteristics of Denmark's population and those of other countries. For example, 21.3% to 24.5% of pregnant people in this study had a body mass index (BMI) over 25 compared with . The editorialists also pointed out that obstetric management strategies, such as cervical cerclage, were not reported in the study.

Finally, "the suggestion that reduced physical activity was associated with improvement in extremely preterm birth rates was not clearly supported by current evidence," Nelson and Spong wrote. "Indeed, associated with reductions rather than increases in rates of preterm birth."

"Despite these caveats, a provocative corollary of the findings from [this study] is the potential association of heat and climate exposure with preterm birth," they added. A also found higher risk of preterm birth linked with environmental exposures such as heat, "which are exacerbated by climate change."

Study Details

The study included over 1.1 million pregnancies among 662,338 individuals (median age at pregnancy onset 30 years) recorded in the Danish Medical Birth Register. Pregnancies were excluded if they did not survive to 21 completed weeks of gestation, were aborted, or had missing data. Of these pregnancies, 2,009 extremely preterm births were identified; there were 4,746 very preterm births and 31,348 moderately preterm births.

The overall prevalence of any preterm birth was 3.4%, which, while in line with rates of preterm birth in Denmark, is much lower than that of the U.S., where approximately .

Subgroup analysis by BMI and smoking status found consistent results, Hviid and colleagues noted.

Broken down by month, gestation during January had the lowest risk, which was significantly lower compared with even December and February, while gestation during September, October, and November carried the highest risk for extremely preterm birth.

As for study limitations, "season of pregnancy onset versus season during gestation can be difficult to distinguish in preterm birth studies because of collinearity issues," the authors acknowledged.

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