Association between ambient temperature and hypertensive disorders in pregnancy in China

Hypertensive disorders in pregnancy (HDPs) are leading perinatal diseases. Using a national cohort of 2,043,182 pregnant women in China, we evaluated the association between ambient

temperatures and HDP subgroups, including preeclampsia or eclampsia, gestational hypertension, and superimposed preeclampsia. Under extreme temperatures, very cold exposure during

preconception (12 weeks) increases odds of preeclampsia or eclampsia and gestational hypertension. Compared to preconception, in the first half of pregnancy, the impact of temperature on

preeclampsia or eclampsia and gestational hypertension is opposite. Cold exposure decreases the odds, whereas hot exposure increases the odds. Under average temperatures, a temperature

increase during preconception decreases the risk of preeclampsia or eclampsia and gestational hypertension. However, in the first half of pregnancy, temperature is positively associated with

a higher risk. No significant association is observed between temperature and superimposed preeclampsia. Here we report a close relationship exists between ambient temperature and

preeclampsia or eclampsia and gestational hypertension.

Hypertensive disorders in pregnancy (HDPs) are the most common pregnancy complications. Such disorders occur in an estimated 3–8% of pregnancies worldwide, and the incidence has increased

over time1,2. HDPs place an enormous burden on pregnant women and their offspring and are among the leading causes of maternal and offspring mortality and morbidity, especially in low-income

and middle-income settings3,4. Among pregnant women, HDPs are strongly associated with pregnancy-related diseases5 and future cardiovascular, renal and cerebral diseases6,7,8. Regarding the

fetus, HDPs are major contributors to premature delivery9 and stillbirths as demonstrated in our previous studies10. Therefore, reducing mortality and morbidity from HDPs is a global

priority for women and infant health. Currently, preventive and therapeutic strategies for HDPs are lacking as the mechanism is not completely understood. The risk factors have been

extensively studied, and the known factors include inherited susceptibility11, placental angiogenic dysfunction12, etc. There is a need for a deep understanding of the pathogenesis of HDPs.

In the context of global climate change, accumulating epidemiological evidence indicates that abnormal ambient temperatures could increase the risk of a wide range of cardiorespiratory

diseases13 and perinatal diseases14,15,16,17. As HDPs are considered special cardiovascular diseases occurring during the perinatal period, it is possible that the ambient temperature may

have an important role in modifying the risk of HDPs. Limited studies detecting the associations between meteorological variables and HDPs have been performed. Most previous studies assessed

the effects of seasonal variation on the prevalence of HDPs and obtained remarkably different results. Compared with other seasons, lower prevalence rates of HDPs were reported in women who

delivered in the autumn18,19 or summer20 or conceived in the autumn21. These results suggest that a seasonal driver of HDPs exists that is independent of other factors. The role of the

ambient temperature, which is among the most important variables contributing to seasonal variation, in the development of HDPs has been poorly explored. Recently, a pilot study reported an

association between the ambient temperature and preeclampsia (a subtype of HDP)22. However, the validity of these results is questionable because of potential bias in the analyses23. Our

primary aim is to investigate the associations between HDPs and ambient temperatures. The secondary aim is to identify possible vulnerable populations with the goal of reducing HDPs and

improving maternal and infant perinatal outcomes.

The sociodemographic characteristics of the included women are shown in Table 1. In total, 2,043,182 pregnant women were included during the study period. The median age is 28 years old

(interquartile range 25–31 years old). In total, 1,973,919 pregnant women without complications (96.61%) served as controls. Among the 69,263 women with HDPs (3.39%), 23,704 women had

gestational hypertension (1.16%), 38,166 women had preeclampsia or eclampsia (1.87%), 5453 women had chronic hypertension (0.27%), and 1940 women had superimposed preeclampsia (0.10%). Most

women with HDPs were from level 2 and level 3 hospitals (level 2 and 3 represent the largest hospitals), had more than 4 antenatal care visits, were married, were in the 25–34 or

35–39-years-old age groups, were nulliparous or with 1 parity, birthed singleton infants, did not birth small for gestational age (SGA) infants, and did not birth preterm infants. The women

with HDPs tended to undergo a cesarean section, whereas the normotensive women tended to undergo vaginal delivery. The distributions of the region, fetus’s sex, and season of conception were

similar in each group.

Compared with women in the moderate local temperature range, the adjusted associations between extreme ambient temperatures and HDPs in China are presented in Fig. 1. During preconception,

very cold exposure (below the 5th percentile) increased the odds of preeclampsia or eclampsia (adjusted odds ratio (aOR): 1.22, 95% confidence interval (CI): 1.12–1.32) (Fig. 1a). In the

first half of pregnancy, the impact of extreme temperatures on preeclampsia or eclampsia appeared to be opposite of that during preconception. Very cold (aOR: 0.89, 95% CI: 0.84–0.94) and

moderate cold (between the 5th and 10th percentile) (aOR: 0.86, 95% CI: 0.81–0.92) temperature exposures reduced the odds of preeclampsia or eclampsia, whereas very hot (above the 95th

percentile) (aOR: 1.16, 95% CI: 1.10–1.22) and moderate hot (between the 90th and 95th percentile) (aOR: 1.13, 95% CI: 1.07–1.19) temperature exposures increased the odds of preeclampsia or

eclampsia. Similar associations were observed between extreme ambient temperatures and gestational hypertension (Fig. 1b). No significant association was observed between extreme ambient

temperatures and superimposed preeclampsia (Fig. 1c).

The models were adjusted for the hospital level, antenatal care visits, marital status, region, mother’s education, mother ’s age, parity, number of fetuses, elevation, humidity, and air

pollution exposure. a Preeclampsia or eclampsia; b gestational hypertension; c superimposed preeclampsia. Data are presented as aORs with 95% confidence intervals. Black error bars

correspond to 95% confidence intervals, center for the error bars correspond to points estimate of aORs. Black stars denote p