Supplementary appendix: Oral polio vaccination and hospital admissions with non-polio infections in Denmark: Nationwide retrospective cohort study Signe Sørup, Lone G. Stensballe, Tyra G. Krause, Peter Aaby, Christine S. Benn, and Henrik Ravn Supplementary Methods. Additional doses of OPV Figure S1. Incidence rate and incidence rate ratio according to most recent vaccine and sequence for admissions with subtypes of infections Table S1. Number of admissions and adjusted incidence rate ratio for infectious-disease hospital admissions by type of infection and duration of admission according to the most recent vaccine. Table S2. Incidence rate and incidence rate ratio of hospital admissions with upper respiratory infections, subdivided by diagnosis of otitis media or not, according to the most recent vaccine Results S1: Additional doses of OPV Table S3. Determinants of additional doses of OPV Table S4. Incidence rate and incidence rate ratio for additional doses pf OPV Table S5. Incidence and incidence rate ratio of emergency department visits following unintentional injury according to the most recent vaccine Table S6. Results for interaction between most recent vaccine and sex for admissions due any type of infection Results S2: Sensitivity analyses 1
Supplementary Methods: Additional doses of OPV The study included all children from the main study cohort who had received and who had not received other types of vaccines than OPV following (last date of follow-up, December 31, 2004). We performed the analyses with the following outcomes: admissions with any type of infection, admissions with the 4 subtypes of infections, and emergency department visits following unintentional injury. The analyses was performed both with the second and third dose of OPV (OPV2 and OPV3) as separate groups and as one joint group. For the outcomes of admissions with any type of infection and emergency department visits following unintentional injury, children who had as their most recent vaccine at 36 months of age and who had not received any doses of OPV yet were also included. However, only a limited number of children had DTaP-IPV-Hib3 or + as the most recent vaccine at 36 months of age and these children were not included due to limited power. 2
Figure S1. Incidence rate and Incidence rate ratio according to most recent vaccine and sequence for admissions with upper respiratory infections (a), lower respiratory infections (b), gastrointestinal infections (c), and other types of infections (d). a) Admission with upper respiratory infection Adj. IRR b =0.90 (0.76-1.07) Rate a 2.1 (763/37,065) Adj. IRR b =1.04 (0.93-1.17) Rate a 1.8 (1512/83,263) DTaP-IPV-Hib3 Rate a 2.8 (172/6243) Adj. IRR b =0.94 (0.74-1.19) Rate a 2.0 (132/6656) Adj. IRR b =1.49 (0.94-2.36) Rate a 2.9 (22/770) Adj. IRR b =0.71 (0.47-1.07) + Rate a 1.5 (28/1927) b) Admission with lower respiratory infection Rate a 1.6 (607/37,065) Adj. IRR b =0.95 (0.83-1.08) Rate a 1.3 (1056/83,263) Adj. IRR b =0.76 (0.64-0.92) DTaP-IPV-Hib3 Rate a 2.7 (170/6243) Adj. IRR b =0.77 (0.59-0.999) Rate a 1.5 (101/6656) Adj. IRR b =1.11 (0.59-2.09) Rate a 1.4 (11/770) Adj. IRR b =0.79 (0.52-1.19) + Rate a 1.5 (29/1927) 3
c) Admission with gastrointestinal infection Adj. IRR b =1.00 Rate a 0.7 (0.83-1.21) (247/37,065) Rate a 0.7 (598/83,263) Adj. IRR b =0.88 (0.65-1.18) DTaP-IPV-Hib3 Rate a 0.9 (58/6243) Adj. IRR b =0.91 (0.62-1.33) Rate a 0.8 (52/6656) Adj. IRR b =0.18 (0.02-1.32) Rate a 0.1 (1/770) Adj. IRR b =0.86 (0.48-1.56) + Rate a 0.7 (14/1927) d) Admission with other infections Rate a 1.2 (432/37,065) Adj. IRR b =0.94 (0.80-1.10) Rate a 0.9 (750/83,263) Adj. IRR b =0.98 (0.76-1.24) DTaP-IPV-Hib3 Rate a 1.4 (86/6243) Adj. IRR b =1.09 (0.79-1.51) Rate a 1.2 (78/6656) Adj. IRR b =0.48 (0.18-1.33) Rate a 0.5 (4/770) Adj. IRR b =0.69 (0.39-1.21) + Rate a 0.8 (15/1927) Abbreviations: DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella; OPV, live oral polio vaccine; Adj, adjusted; IRR, incidence rate ratio. a The incidence rate per 100 person years and in brackets the number of admissions and number of person years. b IRRs for the vaccine type the arrow points at relative to the previous vaccine type in the sequence and in brackets 95% CI. Estimated from Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for mother smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of birth, adults in the household, income quintiles for the household, other children in the household, and population density. c P value from a Wald test of the equality of rates for as most recent vaccine in the adjusted model. d P value from a Wald test of the equality of rates for as most recent vaccine in the adjusted model. 4
Table S1. Number of admissions and adjusted incidence rate ratio for infectious-disease hospital admissions by type of infection and duration of admission according to the most recent vaccine. Duration All durations 0-1 days >=2days Upper respiratory infections Number of admissions (%) a 2629 (100%) 1852 (70.4%) 777 (29.6%) Adjusted IRR b DTaP-IPV-Hib3 1 (ref) 1 (ref) 1 (ref) 0.91 (0.77-1.08) 0.99 (0.80-1.23) 0.78 (0.58-1.05) 0.93 (0.79-1.10) 1.03 (0.83-1.27) 0.77 (0.57-1.02) + 0.70 (0.47-1.06) 0.71 (0.43-1.18) 0.69 (0.35-1.38) Lower respiratory infections Number of admissions (%) a 1974 (100%) 982(49.7%) 992 (50.3%) Adjusted IRR b DTaP-IPV-Hib3 1 (ref) 1 (ref) 1 (ref) 0.77 (0.64-0.92) 0.81 (0.62-1.06) 0.73 (0.56-0.93) 0.73 (0.61-0.87) 0.73 (0.56-0.95) 0.73 (0.57-0.93) + 0.79 (0.52-1.19) 0.92 (0.53-1.61) 0.65 (0.35-1.20) Gastrointestinal infections Number of admissions (%) a 970 (100%) 537 (55.4%) 433 (44.6%) Adjusted IRR b DTaP-IPV-Hib3 1 (ref) 1 (ref) 1 (ref) 0.86 (0.64-1.15) 1.05 (0.69-1.60) 0.70 (0.46-1.06) 0.89 (0.67-1.18) 1.05 (0.70-1.58) 0.76 (0.51-1.13) + 0.87 (0.48-1.58) 0.94 (0.40-2.17) 0.84 (0.36-1.95) Other infections Number of admissions (%) a 1365 (100%) 696 (51.0%) 669 (49.0%) Adjusted IRR b DTaP-IPV-Hib3 1 (ref) 1 (ref) 1 (ref) 0.97 (0.76-1.23) 1.06 (0.75-1.49) 0.86 (0.61-1.22) 0.94 (0.74-1.20) 0.95 (0.67-1.34) 0.93 (0.66-1.30) + 0.69 (0.39-1.21) 0.48 (0.19-1.24) 0.87 (0.42-1.78) Abbreviations: IRR, incidence rate ratio; CI, confidence interval; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella; OPV, live oral polio vaccine. a The total number of admissions by the four types of admissions add to more than the total number of admissions, as admissions may have more than one ICD-10 diagnosis code, and ICD10 codes from more than one type of infection were included in both groups. b Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for mother smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of birth, adults in the household, income quintiles for the household, other children in the household, and population density. 5
Table S2. Incidence rate and incidence rate ratio of hospital admissions with upper respiratory infections, subdivided by diagnosis of otitis media or not, according to the most recent vaccine. Admissions per 100 person-years (Admissions/ Personyears) Unadjusted IRR a Adjusted IRR b a) All upper respiratory infections c DTaP-IPV-Hib3 2.7 (179/6587) 1 (ref) 1 (ref) 2.1 (802/39,057) 0.76 (0.65-0.90) 0.90 (0.76-1.07) 1.8 (1681/91,786) 0.73 (0.62-0.86) 0.93 (0.79-1.10) + 1.5 (29/1979) 0.61 (0.41-0.90) 0.71 (0.47-1.05) b) Otitis media (ICD-10 codes DH65.0-DH66.9) c DTaP-IPV-Hib3 1.0 (66/6587) 1 (ref) 1 (ref) 0.6 (229/39,057) 0.57 (0.43-0.75) 0.71 (0.53-0.95) 0.5 (456/91,786) 0.58 (0.44-0.76) 0.81 (0.60-1.08) + 0.4 (7/1979) 0.44 (0.20-0.96) 0.53 (0.24-1.19) c) Other types of upper respiratory infections c DTaP-IPV-Hib3 1.7 (113/6587) 1 (ref) 1 (ref) 1.5 (573/39,057) 0.88 (0.71-1.08) 1.01 (0.82-1.24) 1.3 (1225/91,786) 0.82 (0.67-1.01) 1.00 (0.82-1.23) + 1.1 (22/1979) 0.70 (0.44-1.12) 0.81 (0.51-1.28) Abbreviations: IRR, incidence rate ratio; CI, confidence interval; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella; OPV, live oral polio vaccine. a Cox proportional hazards model with age as underlying time and stratified by date of birth thereby controlling for age and season. b Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for maternal smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, parental place of birth, adults in the household, other children in the household, and population density. c Information on specific ICD-10 diagnosis codes where only available in data without linkage to highest educational level for the female adult in the household and income quintiles for the household. Therefore these analyses include 141,081 children and in total 2691 admissions with upper respiratory infections, as children with missing information on highest educational level for the female adult in the household and income quintiles for the household are included in these analyses. 6
Results S1: Additional doses of OPV The analyses included 105,936 children from the main study cohort who had received and who had not received other types of vaccines than OPV following ; the analyses of admissions with any type of infection and emergency department visits following unintentional injury also include 24,498 additional children who had as their most recent vaccine at 36 months of age (giving a total of 130,434 children). The distribution of the most recent vaccine according to background factors at 42 and 54 months of age is given in etable3. The results for the analyses of the association between the most recent vaccine and the different outcomes are displayed in Table S4. 7
Table S3. Distribution of most recent vaccine at 42 and 54 months of age according to background factors. % (N) Maternal smoking during pregnancy 42 months of age 54 months of age OPV3 OPV2 % (N) P Value a % (N) % (N) OPV2 % (N) 8 OPV3 % (N) P Value a No 16.6% (13,530) 82.8% (67,715) 0.6% (497) <0.001 8.0% (6476) 21.3% (17,294) 70.7% (57,356) <0.001 Yes 20.3% (4436) 79.1% (17,326) 0.6% (129) 10.4% (2275) 24.6% (5362) 65.0% (14,190) Sex Male 17.5% (9233) 82.0% (43,366) 0.6% (297) 0.123 8.4% (4412) 22.2% (11,654) 69.4% (36,473) 0.234 Female 17.2% (8733) 82.1% (41,675) 0.6% (329) 8.6% (4339) 21.8% (11,002) 69.6% (35,073) Birth weight, gram <=2000 17.9% (286) 81.4% (1302) 0.7% (11) 0.632 9.3% (149) 22.7% (363) 68.0% (1090) 0.343 2001-2500 17.6% (551) 81.7% (2564) 0.7% (22) 8.6% (267) 22.3% (695) 69.2% (2160) 2501-3000 17.3% (2168) 82.0% (10,283) 0.8% (95) 8.5% (1063) 21.6% (2684) 69.9% (8686) 3001-3500 17.4% (5731) 82.0% (26,991) 0.6% (202) 8.7% (2842) 22.1% (7235) 69.2% (22,671) 3501-4000 17.3% (6074) 82.1% (28,775) 0.6% (202) 8.4% (2937) 22.1% (7681) 69.5% (24,171) 4001-4500 17.2% (2542) 82.3% (12,194) 0.5% (77) 8.0% (1182) 22.2% (3265) 69.8% (10,260) >4500 17.2% (614) 82.3% (2932) 0.5% (17) 8.8% (311) 20.6% (733) 70.6% (2508) Gestational age, weeks <37 16.9% (911) 82.3% (4439) 0.8% (43) 0.122 8.9% (477) 20.5% (1106) 70.6% (3804) 0.024 >=37 17.4% (17,055) 82.0% (80,602) 0.6% (583) 8.5% (8274) 22.1% (21,550) 69.4 (67,742) Caesarean section No 17.4% (15,543) 82.0% (73,426) 0.6% (548) 0.579 8.5% (7562) 22.1% (19,696) 69.4% (61,691) 0.025 Yes 17.2% (2423) 82.3% (11,615) 0.6% (78) 8.5% (1189) 21.1% (2960) 70.4% (9855) Chronic diseases No 17.3% (17,322) 82.1% (82,398) 0.6% (608) 0.004 8.4% (8386) 22.0% (21,883) 69.6% (69,258) <0.001 Yes 19.5% (644) 80.0% (2643) 0.5% (18) 10.7% (365) 22.6% (773) 66.8% (2288) Number of admissions due to infections before 24 months of age None 17.0% (14,383) 82.4% (69,476) 0.6% (501) <0.001 8.3% (6956) 21.7% (18,211) 70.0% (58,646) <0.001 One 18.0% (2687) 81.4% (12,183) 0.6% (93) 8.8% (1313) 22.9% (3403) 68.3% (10,143) Two 20.5% (615) 78.9% (2370) 0.6% (18) 10.6% (316) 24.2% (720) 65.2% (1942)
Three or more 21.5% (281) 77.4% (1012) 1.1% (14) 12.7% (166) 24.7% (322) 62.5% (815) Admitted to hospital for any cause within the last month No 17.3% (17,813) 82.1 (84,555) 0.6 (625) <0.001 8.5% (8686) 22.0% (22,530) 69.5% (71,191) 0.009 Yes 23.9% (153) 75.9% (486) 0.2% (1) 11.9% (65) 23.1% (126) 65.0% (355) Maternal age at birth of the child, years <=19 25.2% (390) 73.6% (1139) 1.2% (19) <0.001 15.0% (230) 29.1% (447) 56.0% (860) <0.001 20-24 19.2% (2780) 80.1% (11,630) 0.7% (101) 10.0% (1449) 24.1% (3479) 65.8% (9493) 25-29 16.4% (6373) 83.0% (32,249) 0.6% (228) 7.7% (2985) 21.4% (8242) 70.9% (27,360) 30-34 17.0% (6036) 82.5% (29,354) 0.6% (197) 8.0% (2841) 21.5% (7601) 70.5% (24,907) 35-39 18.0% (2081) 81.4% (9429) 0.6% (67) 9.3 % (1074) 22.0% (2528) 68.7% (7914) >=40 19.6% (306) 79.5% (1240) 0.9% (14) 11.1% (172) 23.3% (359) 65.6% (1012) Highest educational level for the female adult in the household Primary school 21.1% (4621) 78.3% (17,180) 0.7% (143) <0.001 11.3% (2462) 25.3% (5512) 63.5% (13,852) <0.001 High school examination 18.0% (1801) 81.4% (8165) 0.6% (65) 8.7% (867) 22.5% (2236) 68.8% (6840) Vocational training 15.8% (6363) 83.6% (33,600) 0.6% (231) 7.6% (3044) 20.6% (8252) 71.7% (28,683) Bachelor or academy profession 16.2% (4037) 83.2% (20,728) 0.6% (149) 7.4% (1840) 21.0% (5200) 71.5% (17,670) Master s degree or higher 17.5% (1144) 82.0% (5368) 0.6% (38) 8.3% (538) 22.4% (1456) 69.3% (4501) Parental place of birth Denmark 16.7% (14,702) 82.8% (72,993) 0.6% (497) <0.001 8.1% (7075) 21.2% (18,631) 70.7% (62,046) <0.001 Denmark and foreign 20.5% (1630) 78.9% (6274) 0.6% (46) 10.4% (821) 25.2% (1983) 64.4% (5064) Foreign 21.8% (1634) 77.1% (5774) 1.1% (83) 11.7% (855) 27.8% (2042) 60.5% (4436) Adults in the household Two adults 16.9% (16,424) 82.5% (80,199) 0.6% (577) <0.001 8.2% (7874) 21.7% (20,975) 70.1 (67,676) <0.001 Single parent 24.0% (1542) 75.3% (4842) 0.8% (49) 13.6% (877) 26.2% (1681) 60.2% (3870) Income quintiles for the household 1 st (lowest) 22.6% (3633) 76.6% (12,315) 0.8% (133) <0.001 12.6% (2019) 26.6% (4247) 60.8% (9699) <0.001 2 nd 18.7% (3646) 80.7% (15,717) 0.6% (117) 9.4% (1828) 23.6% (4579) 66.9% (12,960) 3 rd 16.6% (3552) 82.8% (17,693) 0.5% (112) 7.7% (1643) 21.5% (4558) 70.8% (15,012) 4 th 15.3% (3526) 84.1% (19,415) 0.6% (138) 7.1% (1622) 20.0% (4584) 73.0% (16,750) 9
5 th (highest) 15.3% (3609) 84.2% (19,901) 0.5% (126) 7.0% (1639) 20.0% (4688) 73.0% (17,125) Other children in the household No 15.7% (6889) 83.7% (36,607) 0.6% (257) <0.001 7.4% (3209) 20.6% (8922) 72.0% (31,218) <0.001 Yes 18.5% (11,077) 80.9% (48,434) 0.6% (369) 9.3% (5542) 23.0% (13,734) 67.7% (40,328) Population density, inhabitants per km 2 <50 15.7% (1175) 83.9% (6297) 0.4% (29) <0.001 7.2% (537) 20.2% (1516) 72.6% (5437) <0.001 50-499 16.6% (10,387) 82.8% (51,755) 0.6% (390) 8.0% (4977) 21.4% (13,307) 70.6% (43,822) 500-1999 17.4% (3321) 82.1% (15,696) 0.5% (98) 8.8% (1663) 21.9% (4154) 69.3% (13,158) 2000-4999 20.0% (909) 79.4% (3617) 0.6% (27) 9.8% (444) 24.5% (1111) 65.7% (2976) >=5000 21.9% (2174) 77.3% (7676) 0.8% (82) 11.5% (1130) 26.1% (2568) 62.5% (6153) Abbreviations: OPV, live oral polio vaccine Note: At 42 months of age 103,633 children was included and at 54 months of age 102,953 children was included. a P values from bivariate Χ 2 test. 10
Table S4. Incidence rate and incidence rate ratio for hospital admissions with any type of infection (a), hospital admissions with upper respiratory infections (b), hospital admissions with lower respiratory infections (c), hospital admissions with gastrointestinal infections (d), hospital admissions with other infections (e), and emergency department visits following unintentional injury (f) according to the most recent vaccine for children aged 36 to 60 months. Events per 100 personyears (Events/ Person-years) Unadjusted IRR* Adjusted IRR a) Admissions with any type of infection 3.0 (1506/49,715) 1.00 (0.91-1.11) 0.99 (0.89-1.09) 3.4 (1124/33,130) 1 (ref) 1 (ref) OPV2 2.9 (3029/106,249) 0.84 (0.78-0.90) 0.93 (0.86-1.00) OPV3 2.2 (1430/66,419) 0.73 (0.66-0.81) 0.87 (0.79-0.96) OPV2 or OPV3 2.6 (4459/172,668) 0.82 (0.76-0.88) 0.92 (0.86-0.99) b) Admissions with upper respiratory infections 1.5 (504/33,130) 1 (ref) 1 (ref) OPV2 1.2 (1325/106,249) 0.81 (0.73-0.91) 0.87 (0.78-0.97) OPV3 1.0 (693/66,419) 0.75 (0.65-0.87) 0.87 (0.75-1.01) OPV2 or OPV3 1.2 (2018/172,668) 0.80 (0.72-0.89) 0.87 (0.78-0.97) c) Admissions with lower respiratory infections 0.7 (246/33,130) 1 (ref) 1 (ref) OPV2 0.6 (662/106,249) 0.83 (0.71-0.97) 0.95 (0.81-1.12) OPV3 0.4 (246/66,419) 0.67 (0.53-0.85) 0.84 (0.66-1.06) OPV2 or OPV3 0.5 (908/172,668) 0.80 (0.69-0.94) 0.93 (0.79-1.09) d) Admissions with gastrointestinal infections 0.4 (138/33,130) 1 (ref) 1 (ref) OPV2 0.4 (387/106,249) 0.93 (0.76-1.16) 0.99 (0.80-1.23) OPV3 0.2 (161/66,419) 0.76 (0.56-1.03) 0.84 (0.62-1.14) OPV2 or OPV3 0.3 (548/172,668) 0.90 (0.73-1.11) 0.97 (0.79-1.20) e) Admissions with other infections 0.9 (294/33,130) 1 (ref) 1 (ref) OPV2 0.7 (784/106,249) 0.80 (0.70-0.93) 0.92 (0.79-1.06) OPV3 0.6 (395/66,419) 0.69 (0.56-0.83) 0.86 (0.70-1.05) OPV2 or OPV3 0.7 (1179/172,668) 0.78 (0.68-0.90) 0.91 (0.78-1.04) f) Emergency department visits following unintentional injury 13.6 (6727/49,535) 1.03 (0.98-1.08) 1.02 (0.97-1.07) 14.5 (4778/33,005) 1 (ref) 1 (ref) OPV2 13.9 (14,680/105,839) 0.95 (0.92-0.98) 0.98 (0.95-1.02) OPV3 12.2 (8074/66,183) 0.94 (0.90-0.98) 1.00 (0.95-1.04) OPV2 or OPV3 13.2 (22,754/172,022) 0.95 (0.92-0.98) 0.98 (0.95-1.02) Abbreviations: IRR, incidence rate ratio; CI, confidence interval; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella; OPV, live oral polio vaccine (the number indicate the dose number). *Cox proportional hazards model with age as underlying time and stratified by date of birth thereby controlling for age and season. Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for mother smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 36 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of 11
birth, adults in the household, income quintiles for the household, other children in the household, and population density. This is the joint group of OPV2 and OPV3. 12
Table S5. Incidence and incidence rate ratio of emergency department visits following unintentional injury according to the most recent vaccine. Emergency visits per 100 person-years (Emergency visits / Person-years) Unadjusted IRR a Adjusted IRR b Most recent vaccine DTaP-IPV-Hib3 15.6 (972/6228) 1 (ref) 1 (ref) 14.8 (5565/37,721) 0.95 (0.89-1.02) 0.97 (0.91-1.04) 14.1 (12,640/89,627) 0.90 (0.84-0.97) 0.96 (0.90-1.03) + 15.4 (296/1920) 0.99 (0.87-1.13) 1.02 (0.89-1.16) Abbreviations: IRR, incidence rate ratio; CI, confidence interval; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella; OPV, live oral polio vaccine. a Cox proportional hazards model with age as underlying time and stratified by date of birth thereby controlling for age and season. b Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for mother smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of birth, adults in the household, income quintiles for the household, other children in the household, and population density. 13
Table S6. Results for interaction between most recent vaccine and sex for admissions due any type of infection Admissions per 100 person-years (Admissions/ Person-years) Unadjusted IRR a Adjusted IRR b Characteristics Female DTaP-IPV-Hib3 5.8 (178/3043) 1 (ref) 1 (ref) 4.2 (777/18,511) 0.72 (0.61-0.85) 0.86 (0.73-1.02) 3.6 (1601/44,062) 0.65 (0.56-0.76) 0.83 (0.71-0.98) + 3.2 (29/893) 0.60 (0.40-0.89) 0.72 (0.49-1.08) Male DTaP-IPV-Hib3 8.6 (274/3200) 1 (ref) 1 (ref) 6.0 (1161/19,325) 0.72 (0.63-0.82) 0.85 (0.74-0.98) 5.3 (2439/45,857) 0.66 (0.58-0.75) 0.86 (0.76-0.99) + 5.2 (54/1034) 0.66 (0.49-0.88) 0.78 (0.58-1.06) P equality for 0.918 0.917 P equality for 0.941 0.711 P equality for 0.709 0.748 + Abbreviations: IRR, incidence rate ratio; CI, confidence interval; DTaP-IPV-Hib, inactivated vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b;, live vaccine against measles, mumps, and rubella. a Cox proportional hazards model with age as underlying time scale and stratified by date of birth thereby controlling for age and season. b Cox proportional hazards model with age as underlying time, stratified by date of birth and adjusted for mother smoking during pregnancy, sex, birth weight, gestational age, caesarean section, chronic diseases, number of infectious disease admissions before 24 months of age, admitted to hospital for any cause within the last 30 days, maternal age at birth of the child, highest educational level for the female adult in the household, parental place of birth, adults in the household, income quintiles for the household, other children in the household, and population density. 14
Results S2: Sensitivity analyses During follow-up 7 admissions with vaccine-targeted infections were registered (3 with pertussis, 1 with measles, 2 with mumps, and 1 with Haemophilus influenzae); exclusion of these admissions did not change the result (adjusted IRR for vs. DTaP-IPV-Hib3, 0.86; 95% CI, 0.77-0.95). The results were also similar when admissions and person-years in the week of vaccination were excluded (adjusted IRR for vs. DTaP-IPV-Hib3, 0.84; 95% CI, 0.76-0.93). The analysis that only included the 112,148 (81.6%) children who had all vaccines registered with their own personal registration number showed similar results (adjusted IRR for vs. DTaP-IPV-Hib3, 0.88; 95% CI, 0.78-0.99). 15