Associations of maternal ambient temperature exposures during pregnancy with the risk of preterm birth and the effect modification of birth order during the new baby boom: A birth cohort study in Guangzhou, China

Abstract

Maternal exposures to ambient temperatures during pregnancy may increase the preterm birth (PTB) risk; however, which periods have stronger effects remain controversial. The effects of temperature exposure on PTB in first- and second-born neonate groups may be different during the new baby boom that has followed the Two-child Policy in China. We examined a birth cohort of 4928 pregnant women beginning in 2016 in Guangzhou, China. An inverse distance weighted method was used to estimate the temperature exposure at each individual residential address. A distribution lag non-linear model incorporating a Cox proportional hazard model was employed to estimate the effects of temperature exposure on PTB and test the effects modification of birth order related to the new baby boom. A total of 4101 pregnant women were included, of which 234 (5.7%) experienced PTB. Compared with the mean temperature (23.0 °C), we found a significantly higher risks of PTB associated with high temperatures (i.e, 30 °C [95th centile]) from the 4th to 8th, and 22nd to 27th gestational weeks. A peak effect was found during the 6th week (HR = 1.79, 95% CI: 1.26, 2.54) and 24th week (HR = 1.83, 95% CI: 1.27, 2.62). The risks of PTB were reduced for low temperatures (i.e. 14 °C [5th centile] versus 23.0 °C) from the 2nd to 10th and 20th to 26th gestational weeks, and the negative peak effect was found during the 4th week (HR = 0.43, 95% CI: 0.26, 0.72) and 23rd week (HR = 0.59, 95% CI: 0.43, 0.83). Stratification analyses showed that significant effects of 30 °C versus 23 °C on PTB were observed during the 4th to 8th weeks in the second-born neonate, and the peak effect was found in the 6th week (HR = 2.13, 95% CI: 1.31, 3.47). However, we did not find significant effects of 30 °C during the same weeks in the first-born neonate group. Maternal exposures to higher temperatures during pregnancy may increase the risk of PTB, and lower temperatures may decrease the risk of PTB. Stronger effects of temperature exposures during the first trimester on PTB risk were found among the second-born neonates than among the first-born neonates.

Introduction

Preterm birth (PTB) is the world's single biggest cause of newborn death, and the second leading cause of all child deaths. PTB is defined by the World Health Organization (WHO) as delivery before 37 completed weeks of gestation (Harrison and Goldenberg, 2015; World Health Organization, 2018). The survivors of PTB remain at risk for numerous sequelae from infancy to adulthood, including asthma and other respiratory diseases, neurodevelopmental sequelae, cerebral palsy, visual impairment, hearing loss, epilepsy, learning difficulties and behavioral problems (Saigal and Doyle, 2008; Kutzora et al., 2018). In 2014, approximately 6.9% (1.17 million) of all births were preterm in China, accounting for 7.8% of PTB globally (Chawanpaiboon et al., 2019).

PTB represents more a syndrome that can be influenced at different periods of development, starting from the gametes, to fertilization, decidualization, placentation, as well as hormonal and vascular homeostasis throughout pregnancy (Villar et al., 2012). That the etiology of around half of PTB cases is still unknown. In recent years, several studies have suggested that maternal exposures to ambient temperature during pregnancy might be a risk factor for PTB (Carolan-Olah and Frankowska, 2014; Mohammadi et al., 2019; Schifano et al., 2013; Zhang et al., 2017). Also, air pollution and other environmental contaminants such as PM_2.5, O₃, SO₂ and lead exposure are suspected risk factors (Liang et al., 2019; Cheng et al., 2017).

Fetal development is a critical period with rapid cell proliferation, immature organ development and metabolic changes, all of which make fetuses more susceptible to environmental temperatures. Additionally, pregnant women may have difficulty with thermoregulation and easily become dehydrated at high temperatures, leading to a decrease in uterine blood flow, which may trigger PTB (Basu et al., 2010; Carolan-Olah and Frankowska, 2014).

Many previous studies that estimated the association between temperature exposure and PTB were based on birth registry data, ecological research and retrospective studies which may not be able to sufficiently adjust for confounding factors, such as tea consumption, vitamin consumption, meat consumption, vegetable consumption, and so on (Carolan-Olah and Frankowska, 2014; Mohammadi et al., 2019; He et al., 2016; Zhang et al., 2017). Therefore, more studies are needed to clarify the associations between temperature exposures with PTB risk using more strictly designed methods, such as prospective birth cohort studies.

Finding the periods where temperature exerts a stronger effects of temperature exposures on PTB risk can assist in guiding prenatal care and intervention measures for clinicians. Several previous studies have attempted to identify the stronger effect periods for temperature exposure during pregnancy on the risk of PTB (Basu et al., 2010; Guo et al., 2018; Schifano et al., 2013; Zheng et al., 2018). The commonly used time scales for finding the periods with the stronger effects on PTB risk in previous studies were trimester or month. These studies could not discern fine enough periods for implementing precise clinical interventions, and the periods for stronger effects remain controversial. While a study suggested that the most obvious increase was during the 3 months before pregnancy (Guo et al., 2018), several other studies found that the stronger effects were in the second or the third trimesters (He et al., 2016; Ha et al., 2016). Recently, Wilson et al. proposed a novel distributed lag model that could estimate the weekly-specific association between temperature exposures and PTB (Wilson et al., 2017). In one of our previous studies, we employed this method to assess the association between weekly air pollution exposure and PTB (Wang et al., 2018). Hence, this method could be used to find the periods with the stronger effects for PTB risk, based on weekly temperature exposures during pregnancy.

In 2016, the Chinese government abolished the well-known One-child Policy which had been implemented for 36 years in China. As of 2016, all couples are permitted to have two children, which is known as the Universal Two-child Policy (Peng, 2015). Many couples of reproductive age who already had a child began planning to have a second one. The number of deliveries in hospitals significantly increased, and older women become pregnant. This led to a new baby boom over the past three years (Zhang et al., 2018). It was reported that the Two-child Policy will add 90 million couples having a second child in China. Of these couples, an estimated 40% are over 35 years old, and the women in these couples will face more pregnancy problems (Liu et al., 2019c). High maternal age is a risk factor for adverse pregnancy outcomes such as antepartum haemorrhage, placenta previa, stillbirth, term low birth weight, and PTB (Carolan et al., 2013; Luke and Brown, 2007; Sheen et al., 2018). Also, multipara mothers are more likely to have additional medical problems such as chronic anemia, cesarean delivery, fetal macrosomia, diabetes mellitus, and/or gestational hypertension which are known to influence fetal growth and development and pregnancy outcomes (Aliyu et al., 2005; Alsammani and Ahmed, 2015). Thus, it is reasonable to hypothesize that there is a more pronounced effect of exposure to non-optimal temperatures on PTB risk in the second-born neonate than in the first-born neonate. However, there is no research to estimate the effect modification of birth order (second-born vs first-born) on the association between temperature exposure and PTB. The results could provide useful information that may enable clinicians to better protect pregnant women from ambient temperatures during pregnancy and to further develop public health strategies to promote the health of baby boomers in China.

We analyzed data from the Prenatal Environments and Offspring Health (PEOH) birth cohort study. We aimed to estimate the associations of maternal exposures to ambient temperature during pregnancy with the risk of PTB, finding the periods with the stronger effects to PTB risk, and further test the modifying effects of birth order during the new baby boom on the association between prenatal temperature exposures and PTB.