Table 3. Risk of ADHDa in the exposed group compared with matched unexposed group.
| Characteristics | No. of participants | No. of ADHD/No. of accumulated PY × 10,000 (incidence rate/10,000 PY) | Absolute rate difference/10,000 PY (95% CI) | aHR (95% CI)b | P valuec | |||
|---|---|---|---|---|---|---|---|---|
| Exposed group | Unexposed group | Exposed group | Unexposed group | |||||
| Gender | 0.059 | |||||||
| Women | 36,092 | 36,092 | 302/17.1 (17.6) | 172/17.4 (9.9) | 7.76 (5.28–1.23) | 1.61 (1.61–1.99) | ||
| Men | 57,625 | 57,625 | 1,692/29.7 (57.0) | 1,146/30.1 (38.0) | 18.97 (15.47–22.47) | 1.38 (1.27–1.50) | ||
| Age group at index date, mon | 0.026 | |||||||
| ≤ 47 | 49,360 | 49,360 | 1,300/34.4 (37.8) | 888/35.1 (25.3) | 12.46 (9.81–15.10) | 1.26 (1.15–1.39) | ||
| > 48 | 44,357 | 44,357 | 694/12.4 (55.9) | 430/12.5 (34.4) | 21.52 (16.24–26.80) | 1.58 (1.39–1.79) | ||
| By time since index date, yr | 0.173 | |||||||
| Less than 5 | 61,123 | 61,123 | 1,572/39.7 (39.6) | 1,051/40.4 (26.0) | 13.60 (11.08–16.11) | 1.33 (1.22–1.46) | ||
| 5 and over | 32,594 | 32,594 | 422/7.1 (59.1) | 267/7.2 (37.2) | 21.92 (14.73–29.11) | 1.54 (1.31–1.82) | ||
| Calendar year at index date | 0.219 | |||||||
| 2008 to 2013 | 61,918 | 62,048 | 1,587/39.8 (39.9) | 1,058/40.6 (26.1) | 13.78 (11.26–16.29) | 1.34 (1.26–1.46) | ||
| 2014 to 2018 | 31,799 | 31,669 | 407/7.0 (58.3) | 260/7.0 (37.3) | 21.01 (13.75–28.26) | 1.54 (1.30–1.82) | ||
| Calendar year at birth date | 0.684 | |||||||
| 2008 | 50,140 | 50,140 | 1,150/24.3 (47.3) | 767/24.7 (31.1) | 16.21 (12.70–19.72) | 1.38 (1.24–1.52) | ||
| 2009 | 43,577 | 43,577 | 844/22.5 (37.5) | 551/22.9 (24.1) | 13.42 (10.19–16.65) | 1.45 (1.29–1.63) | ||
| Birth residence | 0.672 | |||||||
| Seoul/Metropolitan | 45,252 | 224,632 | 1,081/22.5 (48.1) | 703/22.8 (30.9) | 17.23 (13.56–20.90) | 1.45 (1.31–1.61) | ||
| City | 36,056 | 181,604 | 675/18.2 (37.2) | 466/18.4 (25.3) | 11.82 (8.19–15.44) | 1.37 (1.20–1.56) | ||
| Rural | 11,446 | 57,219 | 203/5.7 (35.5) | 133/5.9 (22.4) | 13.06 (6.87–19.26) | 1.30 (1.02–1.66) | ||
| Economic status | 0.148 | |||||||
| Low | 9,735 | 9,850 | 251/4.8 (52.1) | 175/5.0 (35.3) | 16.90 (8.59–25.20) | 1.40 (1.13–1.73) | ||
| Middle | 57,429 | 56,898 | 1,198/28.7 (41.8) | 817/28.8 (28.4) | 13.40 (10.34–16.47) | 1.35 (1.23–1.49) | ||
| High | 23,117 | 23,693 | 436/11.6 (37.5) | 274/12.1 (22.6) | 14.89 (10.47–19.30) | 1.58 (1.34–1.86) | ||
| Any perinatal status | 0.806 | |||||||
| Yes | 38,958 | 22,260 | 1,018/22.8 (44.7) | 374/11.4 (32.8) | 11.92 (7.61–16.23) | 1.40 (1.22–1.59) | ||
| No | 54,759 | 71,457 | 976/24.0 (40.6) | 944/36.2 (26.1) | 14.51 (11.47–17.55) | 1.43 (1.30–1.57) | ||
| Disorders related to length of gestation and fetal growth | 0.633 | |||||||
| Yes | 7,028 | 3,441 | 212/4.1 (52.0) | 65/1.8 (36.7) | 15.24 (3.89–26.58) | 1.41 (1.05–1.91) | ||
| No | 86,689 | 90,276 | 1,782/42.7 (41.7) | 1,253/45.8 (27.4) | 14.34 (11.88–16.79) | 1.41 (1.30–1.53) | ||
| Birth trauma | 0.259 | |||||||
| Yes | 1,126 | 919 | 35/0.6 (57.9) | 12/0.5 (25.7) | 32.80 (8.67–56.93) | 2.27 (1.14–4.52) | ||
| No | 92,591 | 92,798 | 1,959/46.2 (42.4) | 1,306/47.1 (27.7) | 14.67 (12.26–17.07) | 1.40 (1.29–1.51) | ||
| Infections specific to the perinatal period | 0.720 | |||||||
| Yes | 16,998 | 13,737 | 437/8.9 (49.0) | 226/7.0 (32.2) | 16.75 (10.52–22.98) | 1.41 (1.18–1.68) | ||
| No | 76,719 | 79,980 | 1,557/37.9 (41.1) | 1,092/40.6 (26.9) | 14.16 (11.57–16.75) | 1.41 (1.29–1.54) | ||
| Congenital malformation | 0.332 | |||||||
| Yes | 25,897 | 8,140 | 728/16.8 (43.3) | 156/4.2 (36.9) | 6.48 (0.11–13.07) | 1.34 (1.11–1.62) | ||
| No | 67,820 | 85,577 | 1,266/30.0 (42.2) | 1,162/43.3 (26.8) | 15.35 (12.57–18.14) | 1.44 (1.32–1.56) | ||
| Admission during the first year after index date | 0.233 | |||||||
| Yes | 20,919 | 11,722 | 577/12.3 (46.9) | 251/7.4 (33.8) | 13.09 (7.43–18.76) | 1.24 (1.04–1.46) | ||
| No | 72,798 | 81,995 | 1,417/34.5 (41.1) | 1,067/40.1 (26.6) | 14.48 (11.81–17.15) | 1.42 (1.30–1.55) | ||
| Outpatient visits during the first year after index date, day | 0.561 | |||||||
| ≥ 25 (median) | 40,707 | 53,120 | 577/15.6 (35.8) | 530/22.3 (22.8) | 11.92 (8.36–15.55) | 1.34 (1.18–1.53) | ||
| < 24 | 53,010 | 40,597 | 1,437/31.2 (46.0) | 788/25.3 (31.1) | 14.86 (11.64–18.07) | 1.32 (1.20–1.46) | ||
ADHD = attention deficit hyperactivity disorder, PY = person-years, HR = hazard ratio, CI = confidence interval, aHR = adjusted hazard ratio.
aADHD was defined as at least a principal diagnosis of 10th revision of the International Classification of Diseases code F90.X after 72 months of age.
bA Cox proportional hazards model was used to assess the relationship between general anesthesia and later development of ADHD. HRs and 95% CIs of ADHD in relation to previous general anesthesia exposure, using time after the index date as the underlying time scale, were calculated, adjusting for sex, age at the index date, calendar year of birth (2008 or 2009), birth weight, birth residence (Seoul/metropolitan, city, or rural area), economic status (low, middle, or high), and perinatal diseases. The first year of follow-up was excluded from all analyses.
cP value was derived from the interaction test by incorporating an interaction term into the Cox model.