Introduction
The ongoing COVID-19 pandemic has spread throughout the world and affected billions of people(1). Various measures have been implemented around the world to control the pandemic, including restricting large social movements and gatherings, closing international and interstate borders, controlling travel, and implementing partial or full lockdown of cities and regions. These measures have effectively controlled the spread of COVID-19 and reduced the anthropogenic emissions of air pollution (2), which have resulted in substantial health benefits (3). However, these measures have also caused huge economic loss, unemployment, shortage of medical resources, and psychological stress, (4-7) which may lead to adverse health outcomes.
Pregnant women and fetuses may be susceptible populations to the effects of lockdown and restriction measures. A few studies have reported that the COVID-19 lockdown measures may increase the risk of adverse birth outcomes such as stillbirth and cesarean delivery (8,9). Preterm birth (PTB) is one of the most important adverse birth outcomes and a major cause of death in children under 5 years of age(10). Several studies have examined the associations of COVID-19 lockdown measures with the risk of PTB, but the results were inconsistent(8,9,11-14). A study in London reported an increase in the incidence of PTB during the COVID-19 pandemic period over the pre-pandemic period(12). Another study conducted in Nepal also observed a greater risk of PTB during the COVID-19 lockdown than before lockdown.(8) In contrast, studies conducted in Denmark and the Netherlands observed a substantial reduction in the risk of PTB during the COVID-19 periods than before lockdown (11,13). The other two studies conducted in China and Botswana did not find any significant association between the COVID-19 lockdown and the risk of PTB (9,14). The inconsistent findings across these studies may be attributable to differences in study design, sample size, demographic characteristics of study subjects, and socioeconomic developments of societies.
Although the aforementioned studies have preliminarily estimated the associations between COVID-19 lockdown and PTB, several research issues or gaps need to be addressed. First, the susceptibility of pregnant women to environmental factors largely depends on the stage of pregnancy (15,16). Previous studies estimated the overall rate of PTB in pregnant women exposed to COVID-19 lockdown measures (8,9,11,12,14,17-19), but did not consider their pregnancy stage when lockdown occurred. This may lead to an underestimation of PTB risk during the lockdown if pregnant women with a gestational age > 36 weeks were also included. Second, lockdown intensity usually varied over time. However, none of previous studies considered the change in intensity of lockdown exposures. Third, previous studies have suggested a seasonal variation in the incidence of PTB (20,21). The seasonal effects should be considered in selecting the control periods for the COVID-19 lockdown. However, some previous studies applied the annual or multiple years’ average incidence of PTB as the reference (9,11,14), which might lead to biased findings. Fourth, the follow-up time (2-4 months) in previous studies was not long enough to capture the birth outcomes of pregnant women who experienced the lockdown in their early pregnancy (8,9,11,12,14).
To fill these research gaps, we comprehensively elucidated the association of the COVID-19 lockdown on gestational length and PTB risk in South China by quantifying the timing and intensity of exposure, considering seasonal effects, and allowing sufficient follow-up time. This study could provide in-depth insights to inform management practices regarding pregnancy and childbirth during and after lockdown.