Exposure assessment
The National Emergency Response Plan for Public Emergencies by the China
State Council defined 4 levels of emergency response: Level I (extremely
serious), Level II (serious), Level III (relatively serious), and Level
IV (common) (22). After the outbreak of COVID-19, the Guangdong
Provincial Government announced a Level
I response on 1/23/2020 and later
degraded the response level to Level II and Level III on 2/24/2020 and
5/9/2020, respectively. The Level III response was maintained after
5/9/2020. During the Level I response, offices, shops, colleges,
schools, childcare facilities, and all other non-essential institutions
were shut down. Residents’ social activities and gathering were
rigorously restricted. Most of the workforce adapted to a new
work-from-home mode due to traffic and mobility restrictions.
Fewer restriction measures were
implemented during the Level II and Level III responses. During the
Level II response, crowded areas were temporarily closed and disinfected
before reopening. During the Level III response, people’s lives
gradually returned to normal. All shopping malls, supermarkets, hotels,
restaurants, and other living areas were reopened with routine
precautionary measures such as wearing masks and practicing social
distancing (Table S1).
We defined the time period with a Level I response (1/23-2/24/2020) as
Level I lockdown. Women who were pregnant during the Level I lockdown
period were defined as the exposed group (N=101900). Women who were
pregnant during the same calendar months in 2015-2019 were defined as
the unexposed group (N=493496). This served to control for the seasonal
effect, as our data indicated a significant variation in PTB rate across
calendar months of conception (Figure S2).
To further explore the potential susceptible exposure window, we divided
the exposed group into 11 subgroups according to their GW on 1/23/2020.
We determined the day of conception based on the gestational length and
date of birth. For example, women who were conceived during the Level I
lockdown period were defined as the first subgroup, and women whose GWs
were less than four weeks on 1/23/2020 were defined as the second
subgroup (Figure S3). The gestational age of women with over 41 GWs was
grouped into 41 weeks. Similarly, the unexposed group was divided into
correspondingly matching subgroups. With each pair of subgroups (exposed
vs unexposed), we estimated the associations of lockdown exposure with
gestational length and PTB.
Restriction measures during the Level II and Level III responses may
also have adverse effects on PTB risk. Therefore, we quantitatively
estimated individual cumulative exposure dose to lockdown by assigning
different weightings to days with different levels of emergency
responses: 1/22/2020 or earlier (no response, weighting=0),
1/23-2/24/2020 (Level I, weighting=3), 2/25-5/9/2020 (Level II,
weighting=2), and 5/10-12/31/2020 (Level III, weighting=1). Moreover, to
account for the potential effect modification by timing of exposure, we
only estimated the cumulative exposure dose in their first 22 GWs, a
conventional cut-off value of the shortest GW for a newborn to survive
with current medical technology (Figure 2) (23). The distribution of the
lockdown exposure dose in the exposed group is shown in Figure S4.