Short-Term Impact of Atmospheric Pollution on Fecundability in a Polluted Area
Supplemental material
ONLINE SUPPLEMENT
Supplementary Table S1: Adjusted effects of atmospheric pollution levels during the 60 days before
the end of the first month of unprotected intercourse on the probability of pregnancy during the first
month of unprotected intercourse (one and two-pollutant models).
Pollutant
(60-day average)
PM2.5
<25 g/m3
25 to 29.9 g/m3
30 to 34.9 g/m3
35 to 39.9 g/m3
40 to 44.9 g/m3
≥ 45 g/m3
Continuous coding d
N (%) a
1-pollutant models
FR b
95% CI
PM2.5 and NO2
FR b
95% CI
201 (29.9)
473 (29.2)
228 (22.4)
211 (23.2)
264 (25.4)
495 (21.8)
1872 (25.3)
1.00
0.66
0.47
0.55
0.53
0.42
0.78
0.47-0.93
0.31-0.71
0.35-0.87
0.34-0.85
0.24-0.74
0.65-0.94
1.00
0.70
0.51
0.67
0.61
0.74
0.84
0.49-1.00
0.32-0.81
0.38-1.20
0.34-1.10
0.36-1.51
0.68-1.04
299 (30.1)
453 (27.6)
597 (25.6)
353 (19.0)
89 (25.8)
1791 (25.6)
1.00
0.89
0.68
0.46
0.47
0.72
0.70-1.14
0.49-0.96
0.29-0.73
0.25-0.89
0.53-0.97
1.00
0.86
0.76
0.45
0.41
0.83
0.67-1.10
0.51-1.13
0.26-0.80
0.20-0.84
0.57-1.19
2-pollutant models c
PM2.5 and SO2
FR b 95% CI
1.00
0.60
0.40
0.39
0.42
0.35
0.78
FR b
NO2 and SO2
95% CI
1.00
0.79
0.54
0.37
0.38
0.73
0.61-1.04
0.35-0.84
0.22-0.63
0.18-0.76
0.53-1.00
0.41-0.88
0.24-0.66
0.21-0.74
0.22-0.80
0.18-0.71
0.63-0.96
NO2
<30 g/m3
30 to 34.9 g/m3
35 to 39.9 g/m3
40 to 44.9 g/m3
≥ 45 g/m3
Continuous coding d
SO2
429 (26.8)
1.00
1.00
1.00
<30 g/m3
362 (29.0)
1.12
0.87-1.43
0.88 0.65-1.17
1.29
0.97-1.71
30 to 39.9 g/m3
166 (24.7)
0.96
0.65-1.42
0.93 0.62-1.40
1.27
0.80-2.03
40 to 49.9 g/m3
3
219
(27.9)
1.13
0.75-1.68
1.27
0.74-2.16
1.60
0.95-2.69
50 to 59.9 g/m
3
399 (22.3)
0.89
0.59-1.35
0.99 0.55-1.75
1.42
0.84-2.39
60 to 69.9 g/m
297 (20.9)
0.92
0.54-1.58
0.86 0.45-1.65
1.23
0.67-2.28
≥ 70 g/m3
Continuous coding d 1872 (25.3)
0.94
0.85-1.04
1.00 0.90-1.12
0.98
0.88-1.09
FR: Fecundability ratio associated with exposure (average of lag-1 and lag-2 exposures). A value below 1 indicates a
decreased fecundability.
a Number of couples (and proportion of pregnancies during the first month of unprotected intercourse).
b FR associated with exposure and adjusted for all factors of model M4: maternal smoking, BMI, maternal age at the start of
the period of unprotected intercourse, education, marital status, parity (primiparous, yes/no), respiratory epidemic in previous
month and time (restricted cubic spline coding with 7 knots).
c Adjusted models (with adjustment factors listed in b) simultaneously including 2 exposure variables, either as categorical or
as continuous variables.
d FRs are reported for an increase by 10 g/m3 in the pollutant level.
1
Figure S1: Map of the city of Teplice (Czech Republic). The arrow indicates the location of the air
pollution monitoring station (coordinates, 50°38'26.485"N, 13°50'4.637"E).
2
Discussing the potential bias due to temporal trends using a simulation approach
It has been argued that direct adjustment for time in retrospective fecundability study can result in
over-adjustment, and that other approaches to estimate any confounding bias by time could be used.31
In this line, we applied the simulation approach described by Weinberg et al.31 To do so, we adapted
this approach originally developed in the case of a binary exposure to the case of a categorical or
continuous exposure variable. We considered a dataset corresponding to our study population, from
which we removed the real exposure variable. For each subject, we then randomly drew an exposure
variable among all possible exposure levels in the time period spanning from 45 days before to 45
days after the starting date of the period of unprotected intercourse; the adjusted association between
this simulated exposure and the occurrence of a pregnancy in the first month of the period of
unprotected intercourse was assessed using the binomial model with a logarithmic link described in
the methods section. The drawing of exposure and model estimation was repeated 1000 times, and the
distribution of the parameters quantifying the association between pregnancy occurrence and the
simulated exposure variable was described. By removing any link between exposure and fecundability
without changing any temporal trend in exposure or fecundability, this approach allowed estimating
the distribution of the parameter associated with exposure under the “null” hypothesis that exposure
has no direct effect on fecundability, but without removing the temporal trends in exposure and in
fecundability. From the comparison of the effect of exposure estimated in the actual dataset with the
distribution of the simulated parameters (Figure S2), an empirical p-value characterizing the
association between exposure and fecundability corrected for temporal trend was obtained. The
median value of the simulated parameters was also reported, as an indication of the direction and the
amplitude of the potential bias.
The results of this simulation study indicated that temporal trends were likely to induce a bias in the
adjusted fecundability ratio associated with the highest category of PM2.5 60-day average
corresponding to a FR of 0.86 (empirical 95% CI, 0.73; 1.02, Figure S2), compared to a FR of 0.75
observed in our adjusted analysis (95% CI 0.57-0.98, model M2 not adjusted for time); after taking
this bias into account, the corrected p-value associated with this exposure category in our adjusted
analysis was 0.100, compared to 0.036 in the original analysis ignoring the potential bias. For the
continuous coding of PM2.5, the corrected p-value was 3.6%, compared to 1.1% in the original analysis
(Table 3, M2).
Figure S2: Distribution of the simulated fecundability ratios associated with PM 2.5 levels in the 60-day period
before the start of the period of unprotected intercourse (1000 simulations). A) FR associated with the category
corresponding to levels above 45 g/m3. The value of 0.75 observed for the exposure category above 45 g/m3
in the real dataset is shown by the red line (the number of simulated values smaller than the one observed is 50,
corresponding to a corrected p value of 10%). B) FR associated with continuous exposure.
3