Clinical Evaluation of a Low Protein Content Formula in the First Months of Life: a RCT

Clinical Evaluation of a Low Protein Content Formula Fed to Full Term Healthy Infants in the First Months of Life: a Randomized Controlled Trial

This study aimed to evaluate the tolerance and safety of a low-protein formula in healthy full-term infants by investigating effects on growth and gastrointestinal tolerance and by identifying any adverse effects.

Study Overview

• Status: Completed
• Conditions: Safety Issues; Infant Nutrition Disorders
• Intervention / Treatment: Dietary supplement: Low protein formula; Dietary supplement: Standard protein formula

Detailed Description

Infants were randomized to receive either a standard protein formula or a low-protein formula. The composition of the low-protein formula vs the standard formula was: energy (65 vs. 68 kcal/100 mL), protein (1.2 vs. 1.7 g/100 mL).

To investigate the safety of the low-protein formula without any bias, a 4-month intervention period was selected during which the infants were fed only formula.

Anthropometric parameters (weight, length, and head circumference) and body composition were assessed at enrollment, at 2 and 4 months' of age. Parents were asked to keep a diary on the occurrence of gastrointestinal symptoms or any other symptoms and were contacted every two weeks either by clinic visits or phone calls.

The reference group was constituted by a cohort of healthy, exclusively breastfed, full-term infants.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20122
    • NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy
• singleton
• full-term infants (gestational age 37/0 to 41/6 weeks)
• birth weight adequate for gestational age (>p10 and <p90 for gestational age) according to the World Health Organization growth charts.

Exclusion Criteria:

• presence of congenital diseases
• presence of chromosomal abnormalities
• presence of conditions that could interfere with growth, such as brain, metabolic, cardiac and gastrointestinal diseases, perinatal infections.
• being born to mother affected by endocrine and/or metabolic diseases
• having a family history of allergic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low protein formula group; Full term healthy infants randomized to receive a low protein formula for the first 4 months of life	Dietary supplement: Low protein formula; Infants were enrolled to receive low protein formula (energy: 65 kcal/100 mL, protein: 1.2 g/100 mL, protein-to-energy ratio:1.9 g/100 kcal, carbohydrates: 8 g/100 mL, fat: 3.1 g/100 mL) for the firsts 4 months of life.
Active Comparator: Standard protein formula group; Full term healthy infants randomized to receive a standard protein formula for the first 4 months of life	Dietary supplement: Standard protein formula; Infants were enrolled to receive standard protein formula (energy: 68 kcal/100 mL, protein: 1.7 g/100 mL, protein-to-energy ratio:2.5 g/100 kcal, carbohydrates: 7.1 g/100 mL, fat: 3.5 g/100 mL) for the firsts 4 months of life.
No Intervention: Breastfeeding group; Breastfed full term healthy infants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate weight	Weight (g) of each baby was measured on an electronic scale accurate to 0.1 g (PEA POD Infant Body Composition System; Cosmed, Concord, CA, US). Body length was measured to the nearest 1 mm on a Harpenden neonatometer (Holtain, Crymych, UK).	enrollment, 2 months and 4 months
Evaluate lenght	Lenght (cm) of each baby was measured according standard procedures.	enrollment 2 months and 4 months
Evaluate head circumference	Head circumference was measured to the nearest 1 mm using non-stretch measuring tape.	enrollment 2 months and 4 months
Evaluate body composition (fat mass and fat free mass)	Body composition [fat mass and fat free mass (g)]was assessed using an air-displacement plethysmography (PEA POD Infant Body Composition System; COSMED, Italy).	enrollment, 2 months and 4 months
Evaluate weight increase	Weight increase (g/day) was calculated as a change in body weight from weight at study enrollment divided by the time interval from enrolment to the assessment at 4 months Fat mass (g/day) and fat free mass (g/day) increases were also calculated.	2 months, 4 months
Evaluate gastrointestinal tolerance	Parents were asked to keep a diary on the occurrence of gastrointestinal symptoms or any other symptoms and were contacted every two weeks either by clinic visits or phone calls. The occurrence of spitting up, vomiting and colic, defined as intermittent attacks of abdominal pain when the baby screamed and drew up his/her legs but was well between episodes, was recorded. Colic was further classified as severe if the episodes were more than twice per day. Daily frequency of stool passage was also collected.	2 months and 4 months
Evaluate occurence of adverse events	Adverse events were assessed based on inquires to the parents and on their daily records.	2 months and 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate body mass index (k/m2: weight/length2)	Body mass index [BMI: (Kg/m2)] was assessed for all infants enrolled at each study points.	enrollment, 2 months and 4 months
Evaluate z-score	Z-scores values for age were then calculated using the z score calculator provided by WHO [WHO Anthro (version 3.2.2, January 2011)].	enrollment, 2 months and 4 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Collaborators: Humana Co.Ltd.
• Investigators: Principal Investigator: Paola Roggero, MD, NICU. Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, Milan, Italy, 20122

Publications and helpful links

General Publications

• Liotto N, Orsi A, Menis C, Piemontese P, Morlacchi L, Condello CC, Gianni ML, Roggero P, Mosca F. Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial. BMC Pediatr. 2018 Feb 13;18(1):59. doi: 10.1186/s12887-018-1046-6. Erratum In: BMC Pediatr. 2018 Apr 12;18(1):135.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimate): January 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Body composition; Growth; Full term healthy infants; Low protein content formula
• Additional Relevant MeSH Terms: Nutrition Disorders; Infant Nutrition Disorders
• Other Study ID Numbers: Low protein formula_RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided