TABLE 1

Characteristics of the Study Population

CharacteristicaCase Subjects (n = 152)Control Subjects (n = 1520)PbExposed (n = 1280)Unexposed (n = 382)Pc
Demographic variables
 Female gender96 (63)960 (63.2)783 (61.2)273 (69.6).002
 Age, median (IQR), y3 (2–6)3 (2–6)4 (2–7)2 (1–4)<.001d
 Age category, y<.001
  1–5 107 (70)1070 (70.4)844 (65.9)333 (85.0)
  6–1035 (23)350 (23.0)342 (26.7)43 (11.0)
  11–15 10 (7)100 (6.6)94 (7.3)16 (4.1)
 Country of origin
  England126 (82)1301 (85.6).24c1087 (84.9)339 (86.5).26
  Northern Ireland7 (5)48 (3.2)48 (3.8)7 (1.8)
  Scotland11 (7)120 (7.9)101 (7.9)30 (7.7)
  Wales9 (6)51 (3.4)44 (3.4)16 (4.1)
 Townsend indexe.73c.44
  140 (26)389 (25.6)337 (26.3)92 (23.5)
  229 (19)266 (17.5)222 (17.3)73 (18.6)
  329 (19)305 (20.1)258 (20.2)77 (19.6)
  422 (14)298 (19.6)248 (19.4)71 (18.1)
  523 (15)213 (14.0)171 (13.4)65 (16.6)
  Missing9 (6)49 (3.2)44 (3.4)14 (3.6)
Comorbidities
 Prematurity5 (3)26 (1.7).1828 (2.2)3 (0.8).07
 Down or Turner syndrome0000
 Personal AIDf4 (3)2 (0.1).002g6 (0.5)0.17
  Psoriasis3 (2)2 (0.1)
  Uveitis1 (1)0
 Any infectionf141 (93)1297 (85.3).011184 (92.5)254 (64.8)<.001
  Upper respiratory tract124 (82)1129 (74.3).041071 (83.7)182 (46.4)<.001
  Lower respiratory tract37 (24)392 (25.8).69412 (32.2)17 (4.3)<.001
  Gastrointestinal29 (19)251 (16.5).42236 (18.4)44 (11.2).001
  Skin and soft tissue35 (23)294 (19.3).26303 (23.9)23 (5.9)<.001
  Urinary tract6 (4)61 (4.0).9766 (5.2)1 (0.3)<.001
  Bone and joint0000
  Other78 (51)825 (54.3).47774 (60.5)129 (32.9)<.001
 No. of infections, median (IQR)4 (1.5–8)3 (1–6).024 (2–8)1 (0–2)<.001d
Antibiotic exposures
 Any antibiotic prescribed133 (88)1147 (75.5)<.00112800
 Antianaerobic antibioticsf126 (83)1099 (72.3).0041225 (95.7)
  Penicillins124 (82)1082 (72.2).0061206 (72.1)
  Broad-spectrum penicillins14 (9)115 (7.6).47129 (7.7)
  Metronidazole08 (0.5)8 (0.6)
  Clindamycin1 (<1)01 (0.1)
  Other antianaerobich01 (0.1)1 (0.1)
 Non-antianaerobic antibioticsf64 (42)469 (30.9).003533 (41.6)
  Cephalosporins18 (12)143 (9.4).32161 (12.6)
  Macrolides49 (32)329 (21.6).003378 (29.5)
  Sulfonamides25 (16)130 (8.6).001155 (12.1)
  Other non-antianaerobich09 (0.5)9 (0.7)
 Antibiotics with enterohepatic circulationf
  Yes70 (46)492 (32.4)<.001562 (33.6)
  No126 (83)1094 (72.0).0031220 (73.0)
 No. of antibiotic courses prescribed
  Unexposed19 (13)373 (24.5)<.001c0392 (100)
  1–2 courses41 (27)497 (32.7)538 (42.0)
  3–5 courses46 (30)342 (22.5)388 (30.3)
  >5 courses46 (30)308 (20.3)354 (27.7)
 Time between consecutive courses, median (IQR)136 (64–295)133 (68–280).99134 (67–287)
 Other antimicrobial exposure, anyi23 (15)184 (12.1).28182 (14.2)25 (6.4)<.001
Maternal variables
 Maternal AIDf21 (14)115 (7.6)<.001g114 (9.7)22 (6.3).05g
  Arthritis2 (1)4 (0.3)5 (0.4)1 (0.3)
  Connective tissue disease1 (1)3 (0.2)4 (0.3)0
  Diabetes05 (0.3)4 (0.3)1 (0.3)
  IBD1 (1)4 (0.3)4 (0.3)1 (0.3)
  Multiple sclerosis3 (2)7 (0.5)8 (0.7)2 (0.6)
  Psoriasis7 (5)52 (3.4)48 (4.1)11 (3.1)
  Thyroid disease10 (7)38 (2.5)43 (3.7)5 (1.4)
  Uveitis07 (0.5)5 (0.4)2 (0.6)
  Vasculitis06 (0.4)5 (0.4)1 (0.3)
 Missing maternal data13 (9)137 (9.0).85108 (8.4)42 (10.7).001
Other variables
 Cesarean delivery32 (21)227 (14.9).07197 (24.5)62 (25.5).74
  Missing delivery data51 (34)573 (37.7)475 (37.1)149 (38.0)
 Hospitalizationf30 (20)167 (11.0).002177 (13.8)20 (5.1)<.001
  Infection14 (9)69 (4.5).0180 (6.3)3 (0.8)<.001
  JIA17 (11)
  Other18 (12)116 (7.6).07115 (9.0)18 (4.6).10
 No. of outpatient visits in last 2 y, median (IQR)j7 (4–11.5)5 (2–10)<.0016 (2–11)4 (1–7.5)<.001
 Subsequent diagnoses after the study period
  Immunodeficiency0000
  IBD1 (1)01 (0.1)0
  Vasculitis02 (0.1)2 (0.20
  • AID, autoimmune disease; IQR, interquartile range.

  • a All statistics are expressed as n (%) unless otherwise stated.

  • b All P values were obtained from univariable conditional logistic regression models.

  • c P value signifies overall χ2 except as otherwise noted.

  • d P values were obtained by Wilcoxon rank-sum testing.

  • e Geography-based deprivation index; higher index score means more deprived.

  • f Some subjects had >1 type.

  • g P value represents comparison of main category.

  • h Other antianaerobic antibiotics: tetracyclines, glycopeptides (oral vancomycin), carbapenems, cefoxitin (all other cephalosporins categorized as non-antianaerobic). Other non-antianaerobic antibiotics: fluoroquinolones, all other antibiotic classes.

  • i Other antimicrobial agents, including antifungal, antiviral, and antimycobacterial drugs.

  • j Total outpatient visits during 2-year period starting 2.5 years before JIA diagnosis.