Table 1.
Randomised trials of interventions aiming for approximately 3 vs. 4 g·kg−1·d−1 IVN protein in the first week after birth.
| First Author Participants Country |
n | Protein Intake Control Group g·kg−1·day−1 * | Protein Intake Intervention Group g·kg−1·day−1 * |
Amino Acid Solution | Primary Outcome | Outcomes, Conclusions and Other Details |
|---|---|---|---|---|---|---|
| Tan <29 weeks UK [118,137] |
114 | ~2.3 | 2.6 | Not specified | Head growth at 36 weeks | No difference in total brain volume on MRI at 40 weeks. Follow up rate 64% at 9 months. MDI and PDI correlated significantly with energy deficit at 28 days of age. Bayley II assessor not blinded to group allocation. |
| Blanco <1000 g USA [160] |
32 | 2.9 | 3.7 (day 7) | Aminosyn | Mean serum potassium during first 3 days | Follow up rate 63% at 2 years. Bayley II PDI scores similar, but lower MDI score at 18 months in the high AA group. No difference at 24 months. No differences in cerebral palsy, blindness or early childhood intervention between groups at any age. More babies ≤24 weeks’ gestation allocated to higher protein group. |
| Burattini <1250 g Italy [161] |
114 | ~2.5 | ~3.0 | TrophAmine | Weight and weight <10th centile at 36 weeks | Follow up rate 87% at 2 years. No difference in Bayley III scores. Caregivers aware of group allocation. |
| Morgan (SCAMP) <1200 g or <29 weeksUK [116,162] |
150 | 2.4 week 1 3.0 week 2 |
2.8 3.6 |
Vaminolact | Change in HC at 28 days postnatal age and 36 weeks | Follow up rate 62%. No difference in Bayley III assessments at 2 to 3.5 years. High protein group had higher HC z-score at 36 weeks (difference 0.40 95% CI 0.005–0.79, p = 0.047). Parents and assessors blinded to group allocation. |
| Vlaardingerbroek <1500 g Netherlands [154,163] | 103 | 2.4 + 1.4 g lipid on day 2 or 2.4 + 2–3 g lipid from birth | 3.6 + 2–3 g lipid from birth |
Primène | Composite outcome of death or major disability at 2 years | Follow-up rate 92%. No difference in Bayley III assessments and incidence of major disability between groups at 2 years. At 6 weeks, weight and HC z-scores significantly higher in high protein group. Addition of lipids and extra protein increased the amount of phenylalanine used for protein synthesis. |
| Uthaya (NEON) <31 weeks UK [164] |
133 | 1.7 to 2.7 | 3.6 from day 1 | Vaminolact | Lean body mass | Follow up rate 79%. No significant differences for brain volume. HC at term-equivalent age was smaller in the high protein group (mean difference –0.8 cm, 95% CI–1.5 to–0.1 cm; p = 0.02), but also smaller at baseline. |
| Bellagamba 500–1249 g Italy [165] |
160 | ~2.5 | ~3.5 | TrophAmine | Weight gain from birth to 1800 g | Follow-up rate >90%. No differences in Bayley III scores at 2 years. Neonatologists not blinded to group allocation. IVN + enteral intervention. Difference in protein intakes between groups reached 1 g·kg−1·day−1 on day 4 |
| Balakrishnan <1250 g USA [159] |
168 | day 1–2 day 2–2.5 day 3–3 |
3 3.8 4 |
Premasol | Bayley III at 18–24 months CGA | Follow-up rate 78%. No differences in Bayley III scores at 18–24 months. Largest study to date, single centre. Achieved at least 1 g·kg−1·day−1 difference in protein intakes between groups but for only first 3 days |
Trials are listed in chronological order of publication. Ages are post-menstrual age until term-equivalent and then corrected age unless otherwise specified. * Mean actual total protein intake, AA amino acid, CGA corrected gestational age, CI confidence interval, HC head circumference, MDI Motor Development Index, MRI magnetic resonance imaging, PDI Psychomotor Development Index.