2.1. Study Design and Population
breast-fed
RECRUITMENT
The ALFoNS study is a prospective, double-blinded, randomized controlled, intervention trial (RCT) with parallel design comparing three groups of infants fed either standard infant formula (SF) with total protein content of 2.20 g/100 kcal (10% α-lactalbumin of protein), or reduced protein experimental infant formulas with total protein content of 1.75 g/100 kcal with 27% α-lactalbumin of protein (α-lac-EW), or 1.76 g/100 kcal with 14% α-lactalbumin of protein and reduced level of CGMP (CGMP-RW). Exclusively breast-fed infants served as a reference group (BF). The study was conducted at two study sites: Malmö/Lund from December 2014, and extended to Umeå from June 2018 due to lower recruitment rate than expected. The intervention was completed in March 2020. Infants were recruited by invitation letters sent to all families with a four-week-old infant in Malmö and Lund and surrounding area (~8500 deliveries/year) and in Umeå (~1800 deliveries/year). Interested families were informed about the study by telephone by the study nurses. On meeting the inclusion criteria, the parents were invited to the pediatric research unit at the respective study site. Infants were included from five to eight weeks of age in order not to interfere with the establishment of breastfeeding. Inclusion criteria were healthy term infants (37–42 weeks gestational age) appropriate for gestational age, with a birth weight of 2500–4500 g, i.e., within ±2 SD of the national growth chart. At least one parent should be able to read and communicate in Swedish. At inclusion, infants in the formula groups should be exclusively FF, and infants in the BF group exclusively BF, with the mother’s intention to continue either exclusive formula feeding or breastfeeding until six months of age. However, tiny taste portions of complementary food were allowed from four months of age, in accordance with the Swedish National Food Agency recommendations [