Characteristics of participants
Totally, 2280 subjects were included in this study, 699 in case group and 1581 in control group (Fig. 1). Table 1 showed the characteristics of pregnant women between case and control group. The differences between two groups were statistically significant in maternal age, education, residence, history of parturition, infection during periconception and abnormal prenatal examination, while there was no significant difference in history of abortion.
Table 1
The characteristics of pregnant women between case and control group
Variables, n (%)
|
Case group
|
Control group
|
χ2 value
|
p value
|
(n = 699)
|
(n = 1581)
|
Maternal age
|
|
|
|
|
<25 years
|
217 (31.04)
|
165 (10.44)
|
147.88
|
< 0.001
|
25 ~ 30 years
|
350 (50.07)
|
1009 (63.82)
|
>30 years
|
132 (18.89)
|
407 (25.74)
|
Maternal residence
|
|
|
|
Urban
|
237 (33.91)
|
1094 (69.20)
|
248.45
|
< 0.001
|
Rural
|
462 (66.09)
|
487 (30.80)
|
Maternal education
|
|
|
|
≥college
|
241 (34.48)
|
1237 (78.24)
|
407.12
|
< 0.001
|
<college
|
458 (65.52)
|
344 (21.76)
|
Paternal education
|
|
|
|
|
≥college
|
253 (36.19)
|
1250 (79.06)
|
396.51
|
< 0.001
|
<college
|
446 (63.81)
|
331 (20.94)
|
History of parturition
|
|
|
|
No
|
410 (58.66)
|
1217 (76.98)
|
79.61
|
< 0.001
|
Yes
|
289 (41.34)
|
364 (23.02)
|
History of abortion
|
|
|
|
No
|
422 (60.37)
|
1014 (64.14)
|
2.95
|
0.086
|
Yes
|
277 (39.63)
|
567 (35.86)
|
Infection during periconception
|
|
|
No
|
245 (35.05)
|
787 (49.78)
|
42.44
|
< 0.001
|
Yes
|
454 (64.95)
|
794 (50.22)
|
Abnormal prenatal examination
|
|
|
|
No
|
549 (78.54)
|
1453 (91.90)
|
80.84
|
< 0.001
|
Yes
|
150 (21.46)
|
128 (8.10)
|
Positive events
|
|
|
|
|
No
|
539 (77.11)
|
889 (56.23)
|
90.29
|
< 0.001
|
Yes
|
160 (22.89)
|
692 (43.77)
|
Negative events
|
|
|
|
|
No
|
402 (57.51)
|
1029 (65.09)
|
11.90
|
< 0.001
|
Yes
|
297 (42.49)
|
552 (34.91)
|
Association Between Maternal Life Events And CHD In Offspring
As described in Table 2, the average number of positive life events in the case group was 0.30 ± 0.63, while it was 0.58 ± 0.79 in the control group; the average number of negative life events in the case group was 1.12 ± 2.06, while it was 0.72 ± 1.46 in the control group. After adjusting for the confounders, the risk of CHD in the offspring could be reduced by 48% (OR adj =0.52, 95%CI: 0.44 ~ 0.62) for each additional positive life event during pregnancy, while each additional negative life event occurring in pregnant women could make the risk of their offspring increase by 20% (OR adj =1.20, 95%CI: 1.13 ~ 1.28).
Table 2
The association between maternal life events and CHD in offspring
Life events
|
Case group
|
Control group
|
OR (95%CI) a
|
(n = 699)
|
(n = 1581)
|
Unadjusted
|
Adjusted
|
Continuous variables,\(\stackrel{-}{x}\pm s\)
|
Positive events
|
0.30 ± 0.63
|
0.58 ± 0.79
|
0.46 (0.40, 0.54) **
|
0.52 (0.44, 0.62) **
|
Negative events
|
1.12 ± 2.06
|
0.72 ± 1.46
|
1.26 (1.19, 1.34) **
|
1.20 (1.13, 1.28) **
|
Categorical variables, n (%)
|
Positive events
|
No
|
539 (77.11)
|
889 (56.23)
|
1.00
|
1.00
|
Yes
|
160 (22.89)
|
692 (43.77)
|
0.34 (0.28, 0.42) **
|
0.38 (0.30, 0.48) **
|
Negative events
|
No
|
402 (57.51)
|
1029 (65.09)
|
1.00
|
1.00
|
Yes
|
297 (42.49)
|
552 (34.91)
|
1.70 (1.40, 2.06) **
|
1.64 (1.31, 2.05) **
|
a Logistic model was used for estimating risk of life events with or without adjusting for covariates. Adjusted covariates included maternal age, residence, maternal education, paternal education, history of parturition, history of abortion, infection during periconception, and abnormal prenatal examination |
* p < 0.01; ** p < 0.001 |
According to the occurrence of life events, we analyzed them as binary variables. Among all participants, 852 pregnant women had ever experienced positive life events during pregnancy, 160 in case group (22.89%) and 692 in control group (43.77%); 849 pregnant women had experienced negative life events, 297 in case group (42.49%) and 552 in control group (34.91%). Both of differences between two groups had statistical significance. With confounders adjusted, the pregnant women with positive events experienced had a 62% lower risk of CHD in their offspring than those without (OR adj =0.38, 95%CI: 0.30 ~ 0.48). The pregnant women exposure to negative events were 1.64 times more likely to have CHD in their offspring compared with those without (OR adj =1.64, 95%CI: 1.31 ~ 2.05).
Dose-response association between frequency of life events and CHD in offspring
According to the frequency of life events, we investigated the dose-response association between them and CHD in offspring. As shown in Table 3, a trend of dose-response association was observed (p trend <0.001). For positive events, the odds of CHD in offspring decreased as the increase of event frequency. In contrast with those who had not experienced positive events, those experiencing one event had 66% lower odds, and those experiencing two or more events had 75% lower odds (OR1adj = 0.34, 95%CI: 0.27 ~ 0. 43; OR2adj = 0.25, 95%CI: 0.17 ~ 0. 38). For negative life events, the risk increased along with the accumulation of frequency. After adjusting for the confounders, the odds of CHD in offspring were increased 1.41 times for the pregnant women experiencing 1 ~ 2 negative events (OR1adj = 1.41, 95%CI: 1.10 ~ 1.81), 2.13 times for those with 3 ~ 4 events (OR2adj = 2.13, 95%CI: 1.37 ~ 3.32) and 3.16 times for those with 5 or more events (OR3adj = 3.16, 95%CI: 1.84 ~ 5.43) respectively, in comparison with those without negative events.
Table 3
The dose-response association between frequency of life events and CHD in offspring
Frequency
|
Case group
|
Control group
|
OR (95%CI) a
|
p for trend
|
(n = 699)
|
(n = 1581)
|
Unadjusted
|
Adjusted
|
Positive events
|
0
|
539 (77.11)
|
889 (56.23)
|
1.00
|
1.00
|
< 0.001
|
1
|
121 (17.31)
|
524 (33.14)
|
0.35(0.27, 0.44) **
|
0.34 (0.27, 0.43) **
|
≥ 2
|
39 (5.58)
|
168 (10.63)
|
0.26(0.17, 0.38) **
|
0.25 (0.17, 0.38) **
|
Negative events
|
0
|
402 (57.51)
|
1029 (65.09)
|
1.00
|
1.00
|
< 0.001
|
1 ~ 2
|
196 (28.04)
|
422 (26.69)
|
1.42(1.15, 1.76) *
|
1.41 (1.10, 1.81) *
|
3 ~ 4
|
55 (7.87)
|
84 (5.31)
|
2.32(1.58, 3.39) **
|
2.13 (1.37, 3.32) **
|
≥ 5
|
46 (6.58)
|
46 (2.91)
|
4.36(2.73, 6.96) **
|
3.16 (1.84, 5.43) **
|
a Logistic model was used for estimating risk of life events with or without adjusting for covariates. Adjusted covariates included maternal age, residence, maternal education, paternal education, history of parturition, history of abortion, infection during periconception, and abnormal prenatal examination |
* p < 0.01; ** p < 0.001 |
Modification effect of positive life events on CHD in offspring
Further, we divided the variable into four integrated groups in order to explore modification of positive events: P0N0, P0N1, P1N1 and P1N0. Compared with P0N0 group, the odds of CHD in P0N1 group increased by 41% (OR adj =1.41, 95%CI: 1.08 ~ 1.86), while that in P1N1 group decreased by 32% (OR adj =0.68, 95%CI: 0.50 ~ 0.92) (Table 4). It indicated that positive events could weaken or even modify the risk impact of negative events on CHD in offspring.
Table 4
The modified effect of positive events based on integrated grouping
Positive
|
Negative
|
case group
|
control group
|
OR (95%CI) a
|
events
|
events
|
(n = 699)
|
(n = 1581)
|
Unadjusted
|
Adjusted
|
0
|
0
|
346 (49.50)
|
649 (41.05)
|
1.00
|
1.00
|
0
|
1
|
193 (27.61)
|
240 (15.18)
|
1.51 (1.20, 1.90) †
|
1.41 (1.08, 1.86) *
|
1
|
1
|
104 (14.88)
|
312 (19.73)
|
0.63 (0.48, 0.81) †
|
0.68 (0.50, 0.92) *
|
1
|
0
|
56 (8.01)
|
380 (24.04)
|
0.28 (0.20, 0.38) †
|
0.30 (0.21, 0.43) †
|
a Logistic model was used for estimating risk of life events with or without adjusting for covariates. Adjusted covariates included maternal age, residence, maternal education, paternal education, history of parturition, history of abortion, infection during periconception, and abnormal prenatal examination |
* p < 0.05; ** p < 0.01; † p < 0.001 |
Subgroup Analysis
The adjusted ORs of association between occurrence of positive or negative life events and CHD in offspring by selected covariates were showed in Fig. 2. The protective effects of positive events among pregnant women in each subgroup were observed significantly, demonstrating well stability and consistency of the association between life events and CHD. For negative events, except for two subgroups of those older than 30 years and those with abnormal prenatal examination, the significant risk of negative events for CHD was found in rest of subgroups, implying overall robust association.
In addition, as mentioned above, 3 excluded events about life or work changes were supposed to be regarded as negative events for additional analysis. As shown in Supplemental Table S1, pregnant women with positive events experienced had 60% lower odds of CHD in offspring than those without (OR adj =0.40, 95%CI: 0.32 ~ 0.51), while pregnant women with negative events experienced had a 22% higher odds than those without (OR adj =1.22, 95%CI: 0.98 ~ 1.53). Compared with the results of primary analysis, the adjusted risk effect of negative events was reduced and not statistically significant, but the direction remained same as before.