Comparison 3. PKU participants at diagnosis: Low‐phenylalanine diet versus moderate phenylalanine diet.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Blood phenylalanine level (micromol/l)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 Blood phenylalanine level (0 to 3 months)	1	132	Mean Difference (IV, Fixed, 95% CI)	‐127.10 [‐185.04, ‐69.16]
1.2 Blood phenylalanine levels (7 to 12 months)	1	132	Mean Difference (IV, Fixed, 95% CI)	‐157.3 [‐217.18, ‐97.42]
1.3 Blood phenylalanine level (at 2 years)	1	132	Mean Difference (IV, Fixed, 95% CI)	‐84.70 [‐158.02, ‐11.38]
1.4 Blood phenylalanine level (at 3 years)	1	128	Mean Difference (IV, Fixed, 95% CI)	‐48.40 [‐125.39, 28.59]
1.5 Blood phenylalanine level (at 4 years)	1	127	Mean Difference (IV, Fixed, 95% CI)	‐78.70 [‐174.49, 17.09]
1.6 Blood phenylalanine level (at 5 years)	1	127	Mean Difference (IV, Fixed, 95% CI)	‐72.60 [‐162.35, 17.15]
2 Weight (kg)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1 Weight (0 to 3 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.47, 0.07]
2.2 Weight (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.56, 0.16]
2.3 Weight (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.58, 0.38]
3 Intelligence Quotient (IQ)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1 IQ at 4 years	1	111	Mean Difference (IV, Fixed, 95% CI)	3.00 [‐2.77, 8.77]
3.2 IQ at 6 years	1	132	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐3.41, 7.41]
4 Calorie intake (kcal/kg)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
4.1 Calorie intake (0 to 3 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐11.06, 9.06]
4.2 Calorie intake (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐10.12, 4.12]
4.3 Calorie intake (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐6.0 [‐12.51, 0.51]
5 Protein intake (g/kg)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.1 Protein intake (0 to 3 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.40, 0.40]
5.2 Protein intake (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.33, 0.13]
5.3 Protein intake (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.31, 0.11]
6 Phenylalanine intake (mg/day)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
6.1 At 15 months of age	1	151	Mean Difference (IV, Fixed, 95% CI)	‐64.0 [‐67.54, ‐60.46]
6.2 At 21 months of age	1	138	Mean Difference (IV, Fixed, 95% CI)	‐64.0 [‐68.81, ‐59.19]
6.3 At 27 months of age	1	141	Mean Difference (IV, Fixed, 95% CI)	‐88.0 [‐92.56, ‐83.44]
6.4 At 33 months of age	1	139	Mean Difference (IV, Fixed, 95% CI)	‐73.0 [‐77.85, ‐68.15]
6.5 At 39 months of age	1	134	Mean Difference (IV, Fixed, 95% CI)	‐80.0 [‐84.94, ‐75.06]
6.6 At 45 months of age	1	141	Mean Difference (IV, Fixed, 95% CI)	‐58.00 [‐63.95, ‐52.05]
6.7 At 51 months of age	1	125	Mean Difference (IV, Fixed, 95% CI)	‐83.0 [‐88.97, ‐77.03]
6.8 At 57 months of age	1	119	Mean Difference (IV, Fixed, 95% CI)	‐69.0 [‐75.61, ‐62.39]
6.9 At 63 months of age	1	115	Mean Difference (IV, Fixed, 95% CI)	‐106.0 [‐112.54, ‐99.46]
6.10 At 69 months of age	1	117	Mean Difference (IV, Fixed, 95% CI)	‐77.0 [‐90.18, ‐63.82]