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.

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.

Anthropometric and body composition measurements were performed by three medical investigators who were blinded to allocated treatment.

Full term healthy infants randomized to receive a standard protein formula for the first 4 months of life

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.

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.

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).

Body composition [fat mass and fat free mass (g)]was assessed using an air-displacement plethysmography (PEA POD Infant Body Composition System; COSMED, Italy).

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.

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.

Z-scores values for age were then calculated using the z score calculator provided by WHO [WHO Anthro (version 3.2.2, January 2011)].

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

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.