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Table 2 Stratified meta-analysis of caffeine intake (per 100-mg/day increment) and risk of low birth weight/IUGR/SGA

From: Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis

Characteristics Number of studies Summary RR (95% CI) P-for-difference P-for-heterogeneity I 2(95% CI)
All studies 9 1.13 (1.06 to 1.21)   <0.01 82.4 (65.4 to 89.1)
Region      
 United States 4 1.20 (0.95 to 1.52) Ref. 0.01 75.5 (32.3 to 91.1)
 Europe 5 1.12 (1.05 to 1.19) 0.60 <0.01 87.2 (69.2 to 92.7)
Year of publication      
 In or after 2000 5 1.10 (1.04 to1.16) 0.29a 0.07 53.9 (0.0 to 81.0)
 Before 2000 4 1.27 (1.02 to 1.58)   <0.01 89.1 (74.8 to 95.3)
Study population      
 ≥2,500 6 1.11 (1.04 to1.18) Ref. <0.01 86.0 (68.9 to 91.8)
 <2,500 3 1.28 (1.14 to 1.44) 0.25 0.45 0.0 (0.0 to 89.6)
Study design      
 Cohort 8 1.11 (1.04 to 1.18) Ref. <0.01 81.0 (59.1 to 88.7)
 Nested case-control 1 1.33 (1.16 to 1.52) 0.21 - -
Exposure      
 Caffeine 7 1.13 (1.06 to 1.21) Ref. 0.01 67.4 (0.0 to 83.4)
 Coffee 2 1.16 (0.91 to 1.48) 0.93 <0.01 91.9 (NA)
Outcome b      
 LBW 5 1.12 (1.02 to 1.23) Ref. <0.01 75.8 (40.6 to 90.1)
 IUGR 5 1.12 (1.00 to 1.25) 0.78 0.04 59.5 (0.0 to 82.8)
 SGA 2 1.13 (1.07 to 1.18) 0.85 0.14 53.9 (NA)
Age c      
 <30 years 4 1.17 (1.05 to 1.31) Ref. <0.01 88.6 (73.4 to 95.1)
 ≥30 years 5 1.13 (1.08 to 1.19) 0.54 0.32 15.1 (0.0 to 69.2)
Method of exposure assessment      
 Interviewer-based 5 1.17 (1.01 to 1.36) Ref. 0.01 68.2 (17.9 to 87.7)
 Self-administered 3 1.08 (1.01 to 1.16) 0.42 <0.01 90.7 (70.5 to 95.2)
 NA 1 1.33 (1.16 to 1.52) 0.38 - -
Exposure period assessed b      
 First trimester 3 1.17 (0.90 to 1.53) Ref. <0.01 83.0 (48.0 to 94.4)
 First to second trimesters 2 1.09 (0.99 to 1.21) 0.62 <0.01 95.3 (NA)
 Whole pregnancy 2 1.13 (1.04 to 1.24) 0.99 0.40 0.0 (NA)
 Third trimester 2 1.06 (1.00 to 1.12) 0.64 0.63 0.0 (NA)
 NA 1 1.33 (1.16 to 1.52) 0.51 - -
Adjustment for smoking d      
 Fine 7 1.12 (1.04 to 1.20) Ref. <0.01 82.0 (59.1 to 89.6)
 Crude 2 1.24 (0.89 to 1.72) 0.52 <0.01 91.7 (NA)
Median population caffeine intake      
 <200 mg/d 5 1.15 (1.05 to 1.26) 0.32a 0.02 66.7 (0.0 to 85.1)
 ≥200 mg/d 3 1.10 (1.01 to 1.21)   <0.01 83.9 (51.8 to 94.7)
 NA 1 1.40 (0.84 to 2.32)   - -
  1. a P-value was obtained by modeling year of publication and median of assigned doses as continuous variables; btotal number of study is more than 9 because some studies reported additional (usable) results for a different outcome or exposure period; cmean age <30 years or ≥30 years. If mean age is not available, classification was based on whether the majority of the population (>50%) is <30 years or ≥30 years; dfine adjustment for smoking refers to studies that adjusted for amount of smoking or studies that adjusted for smoking using a biomarker; crude adjustment refers to studies that did not adjust for amount of smoking. I 2, I-squared; IUGR, intrauterine growth restriction; LBW, low birth weight; NA, not available; Ref., reference. RR, relative risk; SGA, small for gestational age.