The Use of Early Fortification in Preterm Infants
Early Fortification to Shorten Birth Weight Recovery Time in Very Preterm or Very Low Birth Weight Infants
Very premature or very low birth weight (VLBW) infants are at risk of suboptimal growth after birth, making adequate nutrition essential. Breast milk alone is insufficient to meet the nutritional needs of premature infants, so fortification is added to breast milk to support catch-up growth. Standard human milk fortification (HMF) is typically started when the feeding volume reaches 100 ml/kg/day, but research suggests that early HMF administration can increase protein intake sooner without negative effects on the infant. Early HMF administration didn't increase the incidence of food intolerance and necrotizing enterocolitis (NEC). Other studies have shown that early fortification increases the rate of early weight gain without increasing the incidence of complications. There is no research in Indonesia comparing the duration of regaining birth weight between early HMF and standard HMF. This study aims to determine the difference in the duration of regaining birth weight in very premature or VLBW infants given early HMF versus standard HMF. The research method is a prospective, randomized, double-blind preliminary study comparing early HMF administration (when feeding volume reached 30 ml/kg/day) with standard HMF (when feeding volume reached 100 ml/kg/day).
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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DKI Jakarta
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Jakarta Pusat, DKI Jakarta, Indonesia, 10430
- Cipto Mangunkusumo Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Very preterm infants (gestational age 28 to <32 weeks) or very low birth weight infants (birth weight 1000 to <1500 grams)
- Infants receiving at least 50% of their daily enteral needs from breast milk
- Infants whose parents provided written informed consent to participate in the study
Exclusion Criteria:
- Infants with major congenital abnormalities
- Infants with grade 2 or grade 3 NEC or spontaneous intestinal perforation (SIP) before the intervention
- Infants who had already achieved return to birth weight (RTBW) before initiation of the intervention
- Infants with insufficient breast milk availability to provide ≥50% of their daily enteral requirements before enrollment
- Infants born to mothers with medical conditions that precluded breastfeeding
- Infants with known cow's milk protein allergy before initiation of the intervention
- Infants who died before initiation of the intervention
- Parents who withdrew informed consent
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Cuidados de apoyo
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Early Fortification Group
Participants were given early fortification when the feeding volume reached 30 ml/kg/day |
In the early fortification group, 1 sachet of HMF was added to 30 ml of breast milk for the first 24 hours. If the feeding tolerance was good, 1 sachet of HMF was then mixed into 25 ml of breast milk. |
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Experimental: Standard Fortification Group
Participants were given standard fortification when the feeding volume reached 100 ml/kg/day |
In the standard fortification group, 1 sachet of HMF was mixed into 25 ml of breast milk starting from the first day of HMF administration. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Return to birth weight
Periodo de tiempo: Body weight will be measured daily from birth until the day the infant first reaches their birth weight. The assessment period is expected to last up to 3 weeks after birth.
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The first day the infants reached their birth weight again |
Body weight will be measured daily from birth until the day the infant first reaches their birth weight. The assessment period is expected to last up to 3 weeks after birth.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants with Feeding Intolerance
Periodo de tiempo: Feeding intolerance will be monitored from the initiation of HMF administration until the day the infant first reaches their birth weight. The monitoring period is expected to last up to 3 weeks after birth.
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Feeding intolerance was defined as inability to tolerate enteral feeding, characterized by a gastric residual volume greater than 50% (with or without regurgitation), vomiting, abdominal distension, decreased frequency of bowel movements, and disruption of the feeding plan. |
Feeding intolerance will be monitored from the initiation of HMF administration until the day the infant first reaches their birth weight. The monitoring period is expected to last up to 3 weeks after birth.
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Number of Participants with Electrolyte Imbalances
Periodo de tiempo: Electrolytes will be assessed once during intervention. Blood sampling will be scheduled by the attending physician. The intervention period starts with HMF administration and ends when birth weight is regained, expected within 3 weeks after birth.
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Electrolyte imbalance was identified when serum levels fell below institutional laboratory reference ranges, with assessments performed for all study subjects. |
Electrolytes will be assessed once during intervention. Blood sampling will be scheduled by the attending physician. The intervention period starts with HMF administration and ends when birth weight is regained, expected within 3 weeks after birth.
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Number of Participants with Necrotizing Enterocolitis
Periodo de tiempo: Necrotizing enterocolitis will be monitored from the initiation of HMF administration until the day the infant first reaches their birth weight. The monitoring period is expected to last up to 3 weeks after birth.
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Necrotizing enterocolitis was defined as a disorder of the intestinal mucosa, clinically manifested by feeding intolerance, bloody stools, and possibly accompanied by changes in abdominal skin color, supported by abdominal X-ray findings consistent with necrotizing enterocolitis. |
Necrotizing enterocolitis will be monitored from the initiation of HMF administration until the day the infant first reaches their birth weight. The monitoring period is expected to last up to 3 weeks after birth.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Putri MT Marsubrin, MD, PhD, FKUI RSCM
Publicaciones y enlaces útiles
Publicaciones Generales
- Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, Chan GM, Blanco CL, Abrams S, Cotten CM, Laroia N, Ehrenkranz RA, Dudell G, Cristofalo EA, Meier P, Lee ML, Rechtman DJ, Lucas A. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010 Apr;156(4):562-7.e1. doi: 10.1016/j.jpeds.2009.10.040. Epub 2009 Dec 29.
- Calkins K, Devaskar SU. Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care. 2011 Jul;41(6):158-76. doi: 10.1016/j.cppeds.2011.01.001.
- Shah SD, Dereddy N, Jones TL, Dhanireddy R, Talati AJ. Early versus Delayed Human Milk Fortification in Very Low Birth Weight Infants-A Randomized Controlled Trial. J Pediatr. 2016 Jul;174:126-131.e1. doi: 10.1016/j.jpeds.2016.03.056. Epub 2016 Apr 23.
- Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, Landoulsi S, Jampathong N, Kongwattanakul K, Laopaiboon M, Lewis C, Rattanakanokchai S, Teng DN, Thinkhamrop J, Watananirun K, Zhang J, Zhou W, Gulmezoglu AM. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019 Jan;7(1):e37-e46. doi: 10.1016/S2214-109X(18)30451-0. Epub 2018 Oct 30.
- Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, Okwaraji YB, Mahanani WR, Johansson EW, Lavin T, Fernandez DE, Dominguez GG, de Costa A, Cresswell JA, Krasevec J, Lawn JE, Blencowe H, Requejo J, Moran AC. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023 Oct 7;402(10409):1261-1271. doi: 10.1016/S0140-6736(23)00878-4.
- Thanigainathan S, Abiramalatha T. Early fortification of human milk versus late fortification to promote growth in preterm infants. Cochrane Database Syst Rev. 2020 Jul 29;7(7):CD013392. doi: 10.1002/14651858.CD013392.pub2.
- Joosten K, Vermeulen M. Principles of feeding the preterm infant. Clin Nutr ESPEN. 2024 Feb;59:320-327. doi: 10.1016/j.clnesp.2023.12.016. Epub 2023 Dec 20. No abstract available.
- Fenton TR, Merlino Barr S, Elmrayed S, Alshaikh B. Expected and Desirable Preterm and Small Infant Growth Patterns. Adv Nutr. 2024 Jun;15(6):100220. doi: 10.1016/j.advnut.2024.100220. Epub 2024 Apr 24.
- Alizadeh Taheri P, Sajjadian N, Asgharyan Fargi M, Shariat M. Is early breast milk fortification more effective in preterm infants?: a clinical trial. J Perinat Med. 2017 Nov 27;45(8):953-957. doi: 10.1515/jpm-2015-0375.
- Gupta G, Murugesan A, Thanigainathan S, Adhisivam B. Does Early Fortification of Human Milk Decrease Time to Regain Birth Weight as Compared to Late Fortification Among Preterm Infants? - A Randomized Controlled Trial. Indian J Pediatr. 2025 Jun;92(6):592-597. doi: 10.1007/s12098-024-05066-5. Epub 2024 Feb 28.
- Marsubrin PMT, Rohsiswatmo R, Sjarif DR. Preterm human milk composition and dietary intake of breastfeeding mothers in the Indonesian population. Paediatr Indones. 2021;61:20-24.
- Gidi NW, Goldenberg RL, Nigussie AK, McClure E, Mekasha A, Worku B, Siebeck M, Genzel-Boroviczeny O, Muhe LM. Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28-36 weeks of gestation: a multicentre study in Ethiopia. BMJ Paediatr Open. 2020 Sep 15;4(1):e000740. doi: 10.1136/bmjpo-2020-000740. eCollection 2020.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- 24-06-0986
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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