Increased late preterm birth risk and altered uterine blood flow upon exposure to heat stress

Abstract

Background: Climate change, in particular the exposure to heat, impacts on human health and can trigger diseases. Pregnant people are considered a vulnerable group given the physiological changes during pregnancy and the potentially long-lasting consequences for the offspring. Evidence published to date on higher risk of pregnancy complications upon heat stress exposure are from geographical areas with high ambient temperatures. Studies from geographic regions with temperate climates are sparse; however, these areas are critical since individuals may be less equipped to adapt to heat stress. This study addresses a significant gap in knowledge due to the temperature increase documented globally.

Methods: Birth data of singleton pregnancies (n = 42,905) from a tertiary care centre in Hamburg, Germany, between 1999 and 2021 were retrospectively obtained and matched with climate data from the warmer season (March to September) provided by the adjacent federal meteorological station of the German National Meteorological Service to calculate the relative risk of heat-associated preterm birth. Heat events were defined by ascending temperature percentiles in combination with humidity over exposure periods of up to 5 days. Further, ultrasound data documented in a longitudinal prospective pregnancy cohort study (n = 612) since 2012 were used to identify pathophysiological causes of heat-induced preterm birth.

Findings: Both extreme heat and prolonged periods of heat exposure increased the relative risk of preterm birth (RR: 1.59; 95% CI: 1.01-2.43; p = 0.045; RR: 1.20; 95% CI: 1.02-1.40; p = 0.025). We identified a critical period of heat exposure during gestational ages 34-37 weeks that resulted in increased risk of late preterm birth (RR: 1.67; 95% CI: 1.14-1.43; p = 0.009). Pregnancies with a female fetus were more prone to heat stress-associated preterm birth. We found heat exposure was associated with altered vascular resistance within the uterine artery.

Interpretation: Heat stress caused by high ambient temperatures increases the risk of preterm birth in a geographical region with temperate climate. Prenatal routine care should be revised in such regions to provide active surveillance for women at risk.

Funding: Found in acknowledgements.

Keywords: Climate change; Heat stress; Pregnancy; Preterm birth; Temperature.

Fig. 1

Overview of births and preterm births, course of ambient temperature, the city of Hamburg with the meteorological station,and schematic overview of the experimental design of the analysis, utilizing data from the registry and PRINCE study. (a) Total number of births (grey bars, left Y axis) and percentage of preterm births (solid black line, right Y axis) per year, documented at the University Medical Centre Hamburg-Eppendorf between 1999 and 2021. (b) Average maximum temperature between March and September in Hamburg, Germany during the period 1999–2021 (black line) and heat map depicting the increase in maximum ambient temperatures. Insert: course of average maximum temperature increase (March–September) per year between 1936 and 1998. The colour codes of the heat maps depict the deviation from the mean for each year. (c) The city of Hamburg with the exact location of the University Medical Centre Hamburg-Eppendorf and the federal meteorological monitoring station. Grey circles represent varying distances from the monitoring station. Percentages indicate the residential addresses of registry study participants. (d) Overview of the study design and schematic depiction of the methodological work flow of the two main analyses.

Fig. 2

Periods of heat stress increase the relative risk of preterm birth, especially during gestation weeks 34–36 + 6 (late preterm birth). Relative risk of preterm delivery after heat exposure. Heat events are defined by the daily maximum temperature (a) or the daily apparent temperature (b) for all preterm births. Heat events defined by the daily maximum temperature (c) or the daily apparent temperature (d), stratified for late preterm births (n = 24,863). The number of preterm births per category is shown on the Y-axis; X-axis is displayed in log scale; RR, 95% CI; Pearson χ2.

Fig. 3

Heat stress particularly affects pregnancies with a female fetus. Relative risk of preterm delivery after heat exposure stratified for fetal sex. Heat events defined by the daily maximum temperature (a) and the daily apparent temperature (b) in pregnancies with a female offspring, and male offspring (c, d) respectively (female n = 12,552, male n = 12,954). The number of preterm births per category and fetal sex is shown on the Y-axis; X-axis is displayed in log scale; RR, 95% CI; Pearson χ2.

Fig. 4

Heat stress prior is associated with an increased placental perfusion and lower peripheral resistance of the uterine artery. Logarithmized pulsatility index (logPI) of the umbilical (a) and uterine (b) artery from heat-exposed and non-heat-exposed pregnant women, measured by ultrasound assessment (n = 386). Representative ultrasound images of high (c) and low PI (d), examined at GA 34–36. Scatter-plots represent median + IQR; unpaired t-test.