Study protocol: optimized complementary feeding study (OTIS): a randomized controlled trial of the impact of a protein-reduced complementary diet based on Nordic foods

Early feeding affects health and development later in life [1]. The positive effects of breastfeeding are well known [2], but less is known about how different types and timing of introduction of complementary foods, i.e. the foods used during the transition from breastfeeding or formula-feeding to family foods affect short- and long-term health [3]. From around 4–6 mo. of age eating habits of infants start to change from a liquid diet of breast milk or infant formula to a more diversified diet, mixing breast milk or formula with increasing amounts of solid foods, ending with the child eating the same food as the rest of the family. During this time of complementary feeding, demands for energy and nutrients remain high, especially during the second half of the first year of life. We and others have shown a link between protein intake during this time period and later risk for overweight [4, 5]. Current dietary recommendations for infants and children suggest lower protein intake compared to previous guidelines [6]. Further, we and others have shown that higher intakes of polyunsaturated fatty acids and lower intakes of saturated fatty acids in the diet of infants improve the blood lipid profile and lower blood pressure, and that these influences track into childhood [7‐10]. These polyunsaturated fatty acids, especially in the long-chain form (LCPUFA) found in fish and fish oils have in some studies also been associated with lower risk of asthma, atopic disease and infections during infancy and childhood [11‐13].

The composition of the complementary food is important also from the perspective of flavour, texture and presentation [14]. Already the foetus experiences different sensations of flavour through the amniotic fluid, reflecting what the mother eats [15]. Through breast milk, this exposure continues as infants encounter different flavours in the milk, depending on the types of food the mother consumes [15]. These processes prime the newborn infant to accept the same types of foods as the mother usually takes, including flavours outside the normal preferences of the infant, i.e. sweet, salty and fatty [16]. Further, the acceptance of different textures of foods changes during infancy. As the oral motor skills of the infant develop, the child is able to handle increasingly lumpy and solid foods. A normally developing infant will have periods of greater acceptance of novel foods both in terms of taste and texture, usually coinciding with the time when complementary foods are introduced [17]. However, this window of opportunity to introduce new foods begins to close, usually around 10–12 mo. of age, when the child grows increasingly suspicious of unfamiliar tastes, i.e. develops food neophobia, but also, if solids have not been introduced at this time, to the texture of common food items. This reluctance to try new food items particularly applies to fruits and vegetables, which have a bitter and sour tastes and need repeated exposures to be learned to be appreciated [18]. Numerous studies have shown that fruits and vegetables are an important part of healthy eating habits during all ages [19], but that the actual intake of these food items among young children is low and the best ways to increase the intake largely unknown [20]. Population-based studies from Sweden and elsewhere have shown that the dietary intake of children is not satisfactory from a public health perspective, with intakes of refined sugars, fatty foods and salt being too high and intakes of fruits and vegetables being too low [21]. A recent report on food habits of Swedish adults from the National Food Agency found the worst food habits among young adults age 18–30 years, especially among young women [22]. This is of concern as this is the age when people start families and possibly transmit their poor eating habits to their children.

The New Nordic Food programme [23] is an initiative that highlights the health, gastronomic and sustainability aspects of foods produced within the Nordic region [24]. The overall aim of the diet is to: a) allow a higher energy intake from plant foods and a lower energy intake from meat, b) consume more sea and lake foods and c) consume more foods from the rural countryside [25]. Compared to the regular Swedish diet, the Nordic diet (ND) stresses higher intakes of regionally produced fruits, berries, vegetables, tubers, and legumes as well as higher intakes of whole-wheat, vegetable fats and oils, fish and egg, and lower intake of sweets, desserts and dairy, meat and poultry products, but at the same time being in line with current dietary recommendations [26]. In adults, studies on ND have shown beneficial effects on weight and metabolic and cardiovascular disease biomarkers of the same magnitude as the Mediterranean diet [27, 28] as well as on total mortality [29]. The diet has also been evaluated in a large intervention study among Danish school children aiming to improve dietary intake, nutrient status, growth, early risk biomarkers for adult chronic disease, well-being and cognitive function [30, 31]. The results show an improved dietary intake including higher intakes of fish and vegetables [31] and metabolic effects such as a decrease in mean arterial blood pressure, decreased total cholesterol and improved insulin resistance [32, 33].

Differences in eating behaviour among infants and children is an issue that influence the risk of future obesity [34]. These patterns evolve already in infancy, where genetic predisposition, e.g. sensitivity to bitter taste [35] combine with natural responses to foods and flavours, actual food exposure and parental feeding practices to form the eating style of the individual [36]. Behavioural patterns in childhood that have specifically linked to later obesity include internal factors such as high enjoyment of food, high food responsiveness, emotional overeating and low responsiveness to internal satiety cues, e.g. high eating speed and low satiety sensitivity and external factors such as parental restriction. These behaviours are important to include when examining effects of different diets on later health outcomes and can be measured by validated questionnaires [37‐39].

The nutrient intake of the infant affects its development, for example an adequate iron intake during the second half year of life increases psychomotor development compared to infants not receiving iron supplementation [40]. Systematic reviews of studies on supplementation with LCPUFAs to healthy term infants have failed to show effects on cognitive development measured with the standardized tests such as Bayley Scales of Infant Development (BSID) [41, 42]. However, in even quite small interventions of LCPUFAs during infancy, using more specific tests of brain development has shown positive both short- and long-term effects [43, 44]. Also, a recent randomized, controlled intervention study supplementing infant formula with bovine milk fat globule membranes (MFGM) found a significant effect on cognitive development [45]. It is of note, that the methodology to measure cognitive and psychomotor development following nutritional interventions in infancy using the BSID has recently been challenged, calling for more sensitive methods, including for example attention free play [46].

The gut microbiota has attracted increasing attention during the last several years as a key player in the pathophysiology of chronic disease [47, 48]. Effects on faecal microbiota composition has been a proposed pathway linking early dietary intake with later metabolic outcomes [49] and the development of overweight and also allergic diseases [50]. With the transition from breast-feeding to complementary feeding the gut microbiota undergoes significant changes where correlations have been found between infancy body mass index (BMI) and the faecal flora [51].

In the present study, we draw from the research outlined above, aiming to improve body composition, metabolic markers, cognitive development, blood pressure, food acceptance and the faecal microbiota composition of young children by using a protein-reduced, ND as a basis for complementary feeding.

The overall aim of the study is to compare the effects of a protein-reduced, Nordic diet (ND) portfolio intervention on body composition, metabolic and inflammatory markers, blood pressure, cognitive development, food acceptance and faecal microbiota composition to conventional complementary feeding from 6 to 18 months of age.

More specifically, we will investigate if a complementary diet:

Primary and secondary outcomes of the study and variables collected on adherence and background factors are shown in Table 1.

The early diet has long-lasting effects on human health. Apart from breastfeeding, little is known about which infant diets would confer long-term health benefits. ND has several potential advantages in this respect, and studies in adults have shown favourable effects on metabolic- and cardiovascular disease markers and mortality similar to those gained through the Mediterranean diet. The present study, using ND as the basis for complementary foods but also reducing the total protein intake, improving fatty acid composition and expanding the introduction of fruits and vegetables into the diet of young children will add vital information in the quest to prevent obesity, dyslipidaemia, insulin resistance, type 2 diabetes, hypertension and cardiovascular disease. If the objectives of the study are reached it will thus serve to improve dietary recommendations to infants in Sweden and worldwide. Strengths of the study include individual randomization of the participants, use of well-validated methods of data collection and analysis and close follow-up and support to the participants through dedicated research staff. Possible limitations include difficulties of the families accepting and adhering to the ND, which may lead to higher drop-out rate in the intervention group. The focus on ND may also skew recruitment away from non-Nordic participants. However, this will most likely not affect the outcomes.

Through early intervention, i.e. already when complementary foods are introduced into the diet of the infant, we believe that we can initiate healthy food preferences from the earliest date, thus optimizing the long-term public health benefits. By adopting the concept of ND we will also add gastronomical aspects to the development of optimal complementary foods as well as support regional food production and contribute to a sustainable environment.