Table 1 Adjusted Cox hazard ratios (HR) and 99% confidence intervals (CI) for the outcomes (columns) (i) psychiatric disorder (ICD-10 F diagnoses), and (ii) psychotropic medication until 2014, in relation to exposure to antibiotics (rows) in fetal life, trimesters 1–3 (i.e. maternal purchase of antibiotic drug at least during pregnancy), among the 990 098 births (1996–2012). Outcomes after birth are considered.

From: Early exposure to antibiotic drugs and risk for psychiatric disorders: a population-based study

Antibiotic drugs

Any F diagnosis

F30–39, F92

F40–43, F93

F50

F51

F84

F90–91

F98

Any psychotropic medication

N05

N06A

N06B

ATC code groups

n = 105641

n = 19149

n = 27164

n = 3320

n = 5092

n = 7495

n = 19706

n = 21857

n = 56340

n = 37491

n = 13050

n = 16722

J01CDF, J01EM, J01C or ABEFGMRX

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

HR

99% CI

No, n = 735730

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

1.00

 

Airway (CDF) n = 245664

1.16

1.14–1.18

1.17

1.12–1.22

1.19

1.15–1.23

1.13

1.02–1.26

1.40

1.29–1.51

1.05

0.98–1.13

1.21

1.17–1.27

1.21

1.17–1.26

1.17

1.14–1.20

1.17

1.13–1.20

1.15

1.10–1.21

1.20

1.15–1.26

Urinary tract, soft tissue (EM) n = 2070

1.20

1.02–1.40

1.41

1.02–1.97

1.30

0.97–1.74

0.94

0.36–2.49

1.15

0.55–2.42

1.49

0.88–2.52

1.53

1.11–2.11

1.15

0.81–1.65

1.18

0.95–1.46

1.13

0.86–1.48

1.09

0.69–1.72

1.29

0.88–1.88

CDF and EMa n = 2470

1.18

1.02–1.36

1.15

0.82–1.61

1.43

1.11–1.85

1.08

0.46–2.54

1.51

0.84–2.74

0.99

0.55–1.78

1.00

0.70–1.44

1.22

0.89–1.68

1.08

0.88–1.32

1.11

0.87–1.43

1.01

0.66–1.55

0.90

0.60–1.35

Narrow spectrum (C) n = 240767

1.12

1.10–1.15

1.12

1.06-1.19

1.13

1.08–1.19

1.12

0.98–1.29

1.32

1.19–1.47

1.00

0.91–1.10

1.17

1.11–1.24

1.14

1.09–1.21

1.16

1.13–1.20

1.17

1.12–1.22

1.12

1.04–1.20

1.18

1.11–1.26

Broad spectrum (ABEFGMRX) n = 20651

1.19

1.14-1.24

1.36

1.24–1.48

1.26

1.17–1.36

1.13

0.90–1.43

1.41

1.17-1.70

1.05

0.89–1.25

1.29

1.17–1.41

1.29

1.17–1.41

1.14

1.07–1.20

1.14

1.06–1.22

1.28

1.15–1.42

1.22

1.10–1.35

  1. Any F diagnosis was found for 10.7% of the cohort and included all ICD-10 F diagnoses
  2. ICD-10 F30-39, F92 (1.9% of the cohort) Mood disorders; F40-43, F93 (2.7%) Anxiety disorders; F50 (0.34%) Eating disorders; F51 (0.51%) Nonorganic sleep disorders; F84 (0.76%) Autism Spectrum Disorder (ASD); F90-91 (2.0%) Attention Deficit Hyperactivity Disorder (ADHD) and Conduct disorders; F98 (2.2%) Other behavioral and emotional disorders with onset usually occurring in childhood and adolescence
  3. Psychotropic medications studied defined according to the Anatomic Therapeutic Chemical (ATC) classification system were found for 5.7% of the cohort and included the following: ATC groups N05 (3.8%) antipsychotics, anxiolytics, hypnotics and sedatives; ATC group N06A (1.3%) antidepressants; ATC group N06B (1.7%) stimulants
  4. Antibiotic drugs (ATC codes):
  5. CDF: Any of J01C, D and/or F, i.e., airway antibiotics against primarily gram-positive bacteria, and no J01EM. EM: Any of J01E and/or M, i.e., urinary tract and soft tissue antibiotics against both gram-positive and gram-negative bacteria, and no J01CDF. J01C: Phenoxymethylpenicillin and penicillins with extended spectrum; J01D: Cephalosporins; J01F: Macrolides; J01E: Sulfonamides and trimethoprim; J01M: Fluoroquinolones.
  6. Narrow spectrum: Only J01C
  7. Broad spectrum: Any of J01A, B, E, F, G, M, R and/or X
  8. Birth-related factors adjusted for: maternal age, parity, maternal smoking during pregnancy [yes/no], mother unmarried [yes/no], mother born elsewhere than Finland [yes/no], cesarean section [yes/no], mother’s inpatient care due to mental health disorders [yes/no], mother’s purchase of psychotropic drugs (N05 or N06) during pregnancy [yes/no], mother’s diagnoses related to systemic inflammatory disorders [yes/no], multiple birth [yes/no], offspring sex, perinatal health problems (birth weight < 2500 grams, gestational age < 37 weeks or small for gestational age according to Finnish sex-specific standards) [yes/no]
  9. aExposure to at least two antibiotic drugs
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