Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study—A Randomized Clinical Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
A Priori Research Hypothesis
2.2. Participants
Randomization
2.3. Nutritional Intervention
2.3.1. Adjusted “Modified” Fortification
- BUN < 10 mg/dL: Protein fortification was increased by one level by adding a protein fortification module [oligopeptides (Clinical Nutrition, SA, Barcelona, Spain) 0.5 g/100 mL, 1 g/100 mL or 1.5 g/100 mL]. Protein fortification was progressively increased (0.5–1–1.5 g/100 mL) each week if BUN levels remained below 10 mg/dL.
- BUN > 16 mg/dL: Protein fortification was decreased by one level if growth was adequate.
- If BUN > 10 mg/dL but growth was inadequate, which was defined as a decrease in the weight z-score on the Fenton curves, an insufficient intake of other macronutrients was inferred, and non-protein kilocalories were supplemented with lipids in the form of medium-chain triglycerides [MCT 1–2 mL/kg (Nutricion Medica, Madrid, Spain)] and glucose polymer powder [0.97 g carbohydrates/g (Fantomalt, Nutricia, The Netherlands) 2 g/100 mL].
2.3.2. Targeted Fortification
2.4. Analysis of Human Milk
2.5. Biochemical Analyses
2.6. Outcomes
- Length and head circumference (HC) growth: Cranial–heel length was measured on a length board in supine position (Añó sayol, Barcelona, Spain), and HC was measured with a non-stretching tape to the nearest 0.5 cm.
- Standard deviation score (SDS) differences: Based on Fenton graphs [41] for weight, length, and HC between the periods studied (SDS different time points—SDS birth).
- Actual enteral macronutrient intake (g/kg/day and Kcal/kg/day).
- Nutritional achievements: initiation of enteral nutrition (hours), exclusive enteral nutrition (150 mL/kg/day) (days), parenteral nutrition cessation (days), start of HM fortification (days), and volume of enteral feeding at the beginning of fortification (mL/kg/day).
- Predominant HM type (>50% of intake during the study period): MOM or DHM.
- Perinatal characteristics and neonatal morbidities: early-onset sepsis [45], intraventricular hemorrhage ≥ grade II [46], white matter injury [47], significant ductus arteriosus [48,49], necrotizing enterocolitis defined as Bell’s stage > 2 [50], retinopathy [51], moderate-severe bronchopulmonary dysplasia [52,53], cholestasis [54], late-onset sepsis [45], and death.
- Neonatal intensive care unit (NICU) and hospital stay (days).
2.7. Sample Size and Statistical Analysis
3. Results
3.1. Nutritional Strategy
3.2. Growth Outcomes
3.3. Biochemical Parameters
3.4. Neonatal Morbidity and Hospital Stay
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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General Characteristics of Study Population | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | p-Value |
---|---|---|---|
Gestational age (weeks) Mean (95% CI) | 27 (26.27, 28.01) | 27 (25.88, 27.79) | 0.64 |
Birth weight (g) Mean (95% CI) | 765 (669.79, 860.74) | 819 (767.77, 870.58) | 0.26 |
Birth weight z-score Mean (95% CI) | −0.9 (−1.42, −0.38) | −0.3 (−0.79, 0.18) | 0.09 |
Length birth (cm) Mean (95% CI) | 32.5 (31.18, 33.82) | 33.5 (32.51, 34.51) | 0.19 |
Length birth z-score Median (95% CI) | −0.8 (−1.42, −0.24) | 0.2 (−0.59, 0.97) | 0.07 |
Head circumference at birth (cm) Mean (95% CI) | 23.3 (22.42, 24.17) | 23.6 (22.96, 24.16) | 0.58 |
Head circumference at birth z-score Mean (95% CI) | −0.9 (−1.49, −0.36) | −0.45 (−0.98, 0.08) | 0.21 |
Male No (%) | 9/15 (60) | 11/23 (47.8) | 0.46 |
Multiple gestation No (%) | 4/15 (26.7) | 11/23 (47.8) | 0.19 |
Umbilical cord pH Median (95% CI) | 7.29 (7.17, 7.38) | 7.33 (7.23, 7.36) | 0.12 |
Initial weight loss (%) Mean (95% CI) | 6.7 (4.30, 9.43) | 6.18 (4.23, 8.12) | 0.73 |
Birth weight regain (day) Median (95% CI) | 6 (4.86, 7.81) | 7 (5.34, 7.96) | 0.47 |
Weight at hospital discharge (g) Mean (95% CI) | 2691 (2364.26, 3017.07) | 2816 (2543.68, 3088.49) | 0.54 |
Weight at hospital discharge z-score Median (95% CI) | −1.9 (−2.5,−1.3) | −1 (−1.45, −0.59) | 0.15 |
Length at hospital discharge (cm) Median (95% CI) | 45 (43.57, 46.50) | 45 (43.96, 46.29) | 0.66 |
Length at hospital discharge z-score Median (95% CI) | −2.4 (−3.13, −1.71) | −2 (−2.32, −1.66) | 0.32 |
Head circumference at discharge (cm) Mean (95% CI) | 33.7 (32.85, 34.45) | 33.2 (32.52, 33.96) | 0.43 |
Head circumference at hospital discharge z-score Mean (95% CI) | −0.85 (−1.5, −0.20) | −0.9 (−1.35, −0.46) | 0.89 |
HM Analyses | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | p-Value | Intake | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | p-Value |
---|---|---|---|---|---|---|---|
Protein HM (g/100 mL) Mean (95% CI) | 1.34 (1.25, 1.45) | 1.27 (1.21, 1.35) | 0.20 | Protein g/kg/day Mean (95% CI) | 5.02 (4.73, 5.30) | 4.48 (4.41, 4.56) | 0.001 |
Lipid HM (g/100 mL) Median (95% CI) | 3.30 (3.16, 3.90) | 3.20 (3.05, 3.34) | 0.10 | Lipid g/kg/day Mean (95% CI) | 7.15 (6.45, 7.85) | 6.56 (6.39, 6.74) | 0.10 |
Carbohydrates HM (g/100 mL) Median (95% CI) | 7.32 (7.23, 7.77) | 7.61 (7.35, 7.79) | 0.80 | Carbohydrates g/kg/day Mean (95% CI) | 15.15 (14.09, 16.22) | 15.15 (14.54, 15.76) | 0.99 |
Energy HM (kcal/100 mL) Median (95% CI) | 65.66 (63.67, 69.96) | 64.08 (62.78, 65.57) | 0.15 | Energy kcal/kg/day Mean (95% CI) | 144.72 (135.62, 153.83) | 137.63 (134.94, 140.32) | 0.13 |
Weight Gain g/kg/day | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | Difference (95% CI) | p-Value |
---|---|---|---|---|
From birth to 28 days from the start of HM fortification Mean (95% CI) | 14.06 (12.31, 15.81) | 13.24 (12.13, 14.36) | 0.82 (−1.19, 2.83) | 0.38 |
From birth to 36 weeks PMA Median (95% CI) | 15.31 (13.37, 16.42) | 14.02 (13.16, 16.41) | 0.64 (−1.17, 2.33) | 0.53 |
From birth to discharge Median (95% CI) | 14.53 (13.01, 15.46) | 14.04 (13.35, 15.12) | 0.37 (−1.47, 1.52) | 0.68 |
During the intervention Mean (95% CI) | 16.33 (15.26, 17.40) | 16.89 (15.44, 18.34) | −0.56 (−2.30, 1.18) | 0.56 |
Length Growth cm/week | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | Difference (95% CI) | p Value | Head Circumference Growth cm/week | Adjusted Fortification (n = 15) | Targeted Fortification (n = 23) | Difference (95% CI) | p Value |
---|---|---|---|---|---|---|---|---|---|
From birth to 28 days from the start of HM fortification Mean (CI 95%) | 0.91 (0.78, 1.05) | 0.86 (0.74, 0.98) | 0.05 (−0.12, 0.23) | 0.536 | From birth to 28 days from the start of HM fortification Mean (CI 95%) | 0.78 (0.65, 0.93) | 0.73 (0.64, 0.83) | 0.06 (−0.10, 0.22) | 0.44 |
From birth to 36 weeks PMA Median (CI 95%) | 0.95 (0.89, 1.08) | 0.88 (0.70, 1.49) | 0.07 (−0.12, 0.20) | 0.38 | From birth to 36 weeks PMA Median (CI 95%) | 0.85 (0.76, 0.94) | 0.86 (0.70, 1.18) | 0.01 (−0.10, 0.13) | 0.86 |
From birth to discharge Median (CI 95%) | 0.91 (0.89, 1.07) | 0.94 (0.79, 1.33) | 0.04 (−0.07, 0.15) | 0.47 | From birth to discharge Median (CI 95%) | 0.83 (0.75, 0.91) | 0.79 (0.67, 1.09) | 0.03 (−0.06, 0.13) | 0.41 |
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Sanchez-Holgado, M.; Saenz de Pipaon, M.; Jimenez, M.C.; Crespo Sanchez, G.; Molero-Luis, M.; Montes, M.T.; Segovia, C.; Losantos-García, I.; Jimenez-Gonzalez, M.; Escribano, E.; et al. Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study—A Randomized Clinical Trial. Nutrients 2024, 16, 2904. https://doi.org/10.3390/nu16172904
Sanchez-Holgado M, Saenz de Pipaon M, Jimenez MC, Crespo Sanchez G, Molero-Luis M, Montes MT, Segovia C, Losantos-García I, Jimenez-Gonzalez M, Escribano E, et al. Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study—A Randomized Clinical Trial. Nutrients. 2024; 16(17):2904. https://doi.org/10.3390/nu16172904
Chicago/Turabian StyleSanchez-Holgado, Maria, Miguel Saenz de Pipaon, Maria Concepcion Jimenez, Gema Crespo Sanchez, Marta Molero-Luis, Maria Teresa Montes, Cristina Segovia, Itsaso Losantos-García, María Jimenez-Gonzalez, Esperanza Escribano, and et al. 2024. "Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study—A Randomized Clinical Trial" Nutrients 16, no. 17: 2904. https://doi.org/10.3390/nu16172904