Bibian van der Voorn

147 GENDER-SPECIFIC HPA AXIS ACTIVITY IN CHILDHOOD D Review Manager 5.3 1 1 Cortisol male-female 1.3 Serum cortisol 8-18yrs of age StudyorSubgroup 8 yr (Apter 1979) 8yr (Lashansky 1991) 8yr (Ong 2004) 9 yr (Ilias 2009) 6-15 yr (Ross 1986) 10yr (Stroud 2011) 11-14 (Tsvetkova 1977) 11y (Elmlinger 2002) 12.5 yr (Susman 1991) 13 yr (Hackney 2003) 13yr (Lashansky 1991) 14.6 yr (Ghaziuddin 2003) 14.7 yr (Huybrechts 2014) 15 yr (Syme 2008) 15.5yr (Lashansky 1991) 16.6 ± 0,5yr (Reynolds 2013) 17 yr (Stupnicki 1995) 8-18yr (Bailey 2013) Total(95%CI) Heterogeneity: Chi² = 876.34, df = 17 (P < 0.00001); I² = 98% Test for overall effect: Z = 11.36 (P < 0.00001) Mean 240 254 210 112.97 74.5 164.4 424.89 341 364.7 397.3 223 1,757.5 299.5 546.3 262 551 347 218.3 SD 80.3 86 58 49.14 35.9 5.9 171.1 113.5 149.5 126.9 74 1,191.9 1.6 140.7 80 154 130 98.9 Total 7 8 423 5 23 39 7 22 56 62 10 12 297 77 13 653 14 370 2098 Mean 226.2 229 215 153.26 80 146.5 408.3 364 344.3 466.3 229 1,914.7 305.6 714.6 279 590.98 397 215.7 SD 109.5 94 69 131.05 44.1 5.99 160 117.3 148.7 162.8 94 1,658.2 1.7 306.24 77 202.79 125 110.7 Total 7 7 347 6 24 30 7 23 52 63 11 9 426 82 8 401 15 369 1887 Weight 0.4% 0.4% 22.4% 0.3% 1.4% 0.9% 0.4% 1.3% 3.2% 3.6% 0.6% 0.6% 7.8% 4.4% 0.6% 29.1% 0.8% 21.7% 100.0% IV,Fixed,95%CI 0.13 [-0.91, 1.18] 0.26 [-0.76, 1.28] -0.08 [-0.22, 0.06] -0.36 [-1.56, 0.84] -0.13 [-0.71, 0.44] 2.98 [2.28, 3.68] 0.09 [-0.95, 1.14] -0.20 [-0.78, 0.39] 0.14 [-0.24, 0.51] -0.47 [-0.82, -0.11] -0.07 [-0.92, 0.79] -0.11 [-0.97, 0.76] -3.67 [-3.91, -3.43] -0.70 [-1.02, -0.38] -0.21 [-1.09, 0.68] -0.23 [-0.35, -0.10] -0.38 [-1.12, 0.35] 0.02 [-0.12, 0.17] -0.39 [-0.46, -0.32] Male Female Std. Mean Difference Risk of bias legend ( A ) Selection bias ( B ) Performance bias ( C ) Detection bias ( D ) Other bias ? ? + ? + ? + + + + + + + + + + + ? + + + ? ? + + ? + + + + + + ? + ? + + + + + + + ? ? + ? + ? + ? + + + + + + + + RiskofBias A B C D Std. Mean Difference IV,Fixed,95%CI -2 -1 0 1 2 Female Male E cortisol+sex+child Review Manager 5.3 1 Cortis l mal -f male 1.6 Urinary cortisol <8 yrs of age StudyorSubgroup 3yr (Lundberg 1981) 4.5yr (Lundberg 1983) 3-4 yr (Wudy 2007) 5-6 yr (Wudy 2007) 5-10 yr (Nakamura 1984) 7-8 yr (Wudy 2007) Total(95%CI) Heterogeneity: Chi² = 11.11, df = 5 (P = 0.05); I² = 55% Test for overall effect: Z = 2.28 (P = 0.02) Mean 3.35 8.5 20.5 30.5 14.8 36.9 SD 1.12 1.8 6.63 10.2 3.6 12.9 Total 4 8 25 25 7 25 94 Mean 2.46 11.9 21.2 25.4 9.98 31.9 SD 0.44 5.5 6.49 7.52 3.2 10.9 Total 9 3 25 25 8 25 95 Weight 5.2% 4.3% 28.6% 27.4% 6.6% 28.0% 100.0% IV,Fixed,95%CI 1.19 [-0.11, 2.49] -1.02 [-2.45, 0.41] -0.11 [-0.66, 0.45] 0.56 [-0.01, 1.13] 1.34 [0.18, 2.50] 0.41 [-0.15, 0.97] 0.34 [0.05, 0.64] Male Female Std. Mean Difference Risk of bias legend ( A ) Selection bias ( B ) Performance bias ( C ) Detection bias ( D ) Other bias ? + + ? + ? + + + + + + + + ? + + + + + + Risk of Bias A B C D Std. Mean Difference IV,Fixed,95%CI -2 -1 0 1 2 Female Male F cortisol+sex+child 30-Oct-20 Review Manager 5.3 1 Cortisol male-female 1.11 Urinary Cortisol Production Rate 8-18yrs of age StudyorSubgroup 8yr (Honour 2007) 9-10 yr (Wudy 2007) 4-15yr (Canalis 1982) 11-12 yr (Wudy 2007) 13 ±3yr (Vaindirlis 2000) 13-14 yr (Wudy 2007) 14-19yr (Nakamura 1984) 15-16 yr (Wudy 2007) 17-18 yr (Wudy 2007) Total(95%CI) Heterogeneity: Chi² = 8.67, df = 8 (P = 0.37); I² = 8% Test for overall effect: Z = 4.31 (P < 0.0001) Mean 2,826.86 35.5 15.2 54.1 94 53.2 40.9 68.5 75 SD 774.81 9.26 6.3 13.8 32 21.4 23 21 25.3 Total 244 25 14 25 12 25 6 25 25 401 Mean 2,557.71 34.9 13 43.6 69 49.5 33.3 65.1 81.1 SD 655.56 12.5 5.6 12.2 33 15.1 3.1 22 32.3 Total 188 25 15 25 10 25 7 25 25 345 Weight 57.7% 6.9% 3.9% 6.4% 2.8% 6.9% 1.7% 6.9% 6.9% 100.0% IV,Fixed,95%CI 0.37 [0.18, 0.56] 0.05 [-0.50, 0.61] 0.36 [-0.38, 1.09] 0.79 [0.22, 1.37] 0.74 [-0.13, 1.61] 0.20 [-0.36, 0.75] 0.45 [-0.66, 1.56] 0.16 [-0.40, 0.71] -0.21 [-0.76, 0.35] 0.32 [0.17, 0.47] Male Female Std. Mean Difference Risk of bias legend ( A ) Selection bias ( B ) Performance bias ( C ) Detection bias ( D ) Other bias + + + + + + + ? ? ? + + + + + ? + ? + + + + + ? + + + + + + + + + + RiskofBias A B C D Std. Mean Difference IV,Fixed,95%CI -2 -1 0 1 2 Female Male FIGURE 3. Forest plots of gender differences per subgroup (Fixed effect analyses) A Salivary cortisol (nmol/L) <8 yr of age B Salivary cortisol (nmol/L) 8–18 yr of age C Serum cortisol (nmol/L) <8 yr of age D Serum cortisol (nmol/L) 8–18 yr of age E 24h-urine cortisol (µg/24h) <8 yr of age F 24h-urine cortisol (µg/24h) 8–18 yr of age Compared to girls, boys <8 yr had 0.21 (0.05 to 0.37) nmol/L ( P = 0.01, I 2 = 48%) higher salivary and 0.18 (0.06 to 0.30) nmol/L ( P < 0.01, I 2 = 94%) higher serum cortisol levels. Between ages 8-18 yr, boys had 0.42 (0.38 to 0.47) nmol/L ( P < 0.01, I 2 = 94%) lower salivary and 0.34 (0.28 to 0.40) nmol/L ( P < 0.01, I 2 = 97%) lower serum cortisol levels. In contrast, free cortisol in 24h-urine was 0.34 (0.05 to 0.64) µg/24h ( P = 0.02, I 2 = 55%) higher in boys aged <8 yr and 0.32 (0.17 to 0.47) µg/24h ( P <