OTIS - Optimized Complementary Feeding Study
Condition: Infant Development; Body Composition, Beneficial; Dietary Modification
Study type: Interventional

Summary: 
      Dietary factors during infancy, e.g. high intakes of protein, fast carbohydrates and
      saturated fat increase the risk of adult obesity, type 2 diabetes and hypertension. However,
      current dietary recommendations to infants are based on traditions and experiences whereas
      research is basically lacking.

      Towards the end of the first year of life the infant will normally become increasingly
      suspicious towards fruits and vegetables. However, these foods are an important part of
      healthy eating. When and how these food items should be introduced into the diet of young
      children is unclear.

      New Nordic Diet, an initiative from the Nordic Council of Ministers calls for a larger intake
      of fruits, vegetables, whole grain, fish and game. In adults such diet improves weight and
      biomarkers of insulin resistance and cardiovascular disease. Since dietary preferences are
      founded early in life it is logical to introduce such a diet already when the child is
      starting complementary foods.

      In a randomized controlled study from 6 mo of age, we want to explore if a Nordic
      complementary diet with lower protein intake, more vegetable fats and a systematic
      introduction of fruits and greens will improve body composition, metabolic biomarkers, the
      composition of faecal microbiota (associated with obesity), cognitive development and the
      consumption of foods that can lay the foundation for better long-term diet. If the study has
      the expected results, these will have a direct impact on the dietary habits of Swedish
      children during infancy and childhood and thus their long-term health.
    

Detailed description: 
      Introduction Evidence is accumulating that early feeding affects health and development later
      in life. The positive effects of breast feeding are well known, but less is known on how
      different types and timing 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.
      During the time of complementary feeding, the 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. Earlier studies
      have implicated very high protein intakes during infancy but the latest dietary
      recommendations for infants and children suggest lower intakes, which may have contributed to
      the decreasing prevalence of obesity seen in some countries. Early introduction of
      carbohydrate-rich complementary foods has also been associated to alterations leading to
      later obesity and insulin resistance. Finally, 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 blood lipids and that these influences track into childhood.

      The composition of the complementary food is important also from the perspective of food
      flavour, texture and presentation. Experiences of flavour during foetal and breast feeding
      period prime the newborn infant to accept the same types of foods as the mother usually
      takes, including foods with flavours outside the normal preferences of the infant, i.e.
      sweet, salty and fatty. Also the acceptance of different textures of foods changes during the
      infancy year. 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 flavour and texture, usually coinciding with the
      time when complementary foods are introduced. However, this window of opportunity to
      introduce new foods begins to close around 10-12 mo. of age, when the child grows
      increasingly suspicious of unfamiliar tastes, i.e. food neophobia, but also, if solids
      haven't been introduced at this time, to the texture of common food items. Studies have shown
      that the types and numbers of different foods that a child accepts can be influenced by the
      manner and frequency of how they are introduced during this time. Numerous studies have shown
      that fruits and vegetables are an important part of healthy eating habits in all ages, but
      that the actual intake of these food items among young children is low. Instead,
      population-based studies from Sweden 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.

      In 2005 the Nordic Council of Ministers launched the New Nordic Food programme. This
      initiative highlights the health, gastronomic and sustainability aspects of foods produced
      within the Nordic region. Compared to the regular Swedish diet, the Nordic diet (ND) stresses
      higher intakes of regionally produced fruits, berries, vegetables, tubers, and legumes,
      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. In adults, studies on ND have shown beneficial effects
      on weight and metabolic and cardiovascular disease markers of the same magnitude as e.g. the
      Mediterranean diet.

      We aim to improve body composition, metabolic markers and the faecal microbiota composition
      of young children by using ND as a basis for complementary foods, with its emphasis on
      regionally produced fruits, berries, vegetables, tubers and legumes, also increasing the
      intake of fish and vegetable fats and oils, particularly using rapeseed oil but decreasing
      total protein intake. Effects on faecal microbiota composition have been a proposed pathway
      linking early dietary intake with later metabolic outcomes.

      Relevance The early diet has longstanding effects on human health. Apart from breastfeeding
      little is known on 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 small children is the first study of
      its kind and will add vital information in the search to prevent obesity, dyslipidaemia,
      insulin resistance, type 2 diabetes, hypertension and cardiovascular disease and will have
      implications for future national and international dietary recommendations to young children.
      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 maximizing the long-term public health benefits of healthy eating. 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.

      Objectives The overall aim of the study is to compare the effects of a ND portfolio
      intervention on body composition, metabolic markers, blood pressure and faecal microbiota
      composition to conventional complementary feeding from 6-18 months of age.

      More specifically, we will investigate if:

        1. A complementary diet lower in protein (total reduction 30%) will affect growth, body
           composition, i.e. reduce total body fat mass and improve metabolic markers, i.e.
           decrease plasma (P) levels of insulin, glucose and insulinlike growth factor 1 (IGF1)
           without detrimental effects on linear growth.

        2. A complementary diet based on Nordic foods will affect growth, body composition, i.e.
           reduce body fat mass and improve metabolic markers and the faecal microbiota
           composition, i.e. a microbiota composition associated with less obesity and inflammation
           without detrimental effects on linear growth.

        3. Complementary foods with a modified fat intake, i.e. a higher intake of LCPUFA through
           an increased intake of fish and substituting fats and oils found in regular
           complementary foods with milk fat and rapeseed oil will improve body composition,
           metabolic markers, cognitive development and the faecal microbiota composition without
           detrimental effects on linear growth.

        4. A systematic introduction of plant foods from the Nordic diet during weaning will
           increase the acceptance of new fruits and vegetables into the diet of the young child.

      Methods Participants and recruitment Healthy, full-term singletons will be recruited at 4
      months of age. When parents consider it appropriate to introduce complementary foods into the
      diet of their child, but no later than at 6 mo. of age, the child will be randomly allocated
      to one of two study groups, i.e. the Nordic diet group (intervention, ND) or the Regular diet
      group (control). The group allocation will be masked for the participants and researchers.

      Study products All participants will be provided with study products free of charge. In the
      ND group these will be specially prepared, protein-reduced, age-adjusted milk cereal drinks
      (MCDs), baby cereals and baby milk, and commercially available baby foods in glass jars
      (BIG). The control group will be offered commercially available, age-adjusted MCDs, baby
      cereals, baby milk and BIG. All products will be manufactured by Semper AB, Sweden.

      Introduction of complementary feeding The ND group will be given recipes of fruit and
      vegetable purees and instructions how to prepare these recipes. The main ingredients will be
      fruits, berries and vegetables which grow and are available in the Nordic region according to
      a predefined list. These taste meals will be given to the participating infant when the
      parents judge it prudent to start offering the infant other foods beside breast milk or
      formula and the infant is deemed ready by the parent.

      The control group will be given the standard, oral and written advice that is given from
      well-baby clinics to parents when beginning with small taste meals.

      Parental support Parents with children in the ND group will be given support to continue
      following the dietary intervention through social media (Face book). In this forum parents
      can discuss with the study dietician and among themselves, sharing experiences. Parents will
      also have instructional videos on the preparation of certain study foods and recipes.
      Participants will share experiences and other information at their own discretion. No data
      will be collected through this group, but the group may function as a way to inform the
      families on the group on upcoming study events and remind participants to send in e.g.
      questionnaires. Both the intervention and the control group will get monthly telephone calls
      from the research nurse or the study dietician.

      Data collection Main data collection points will be at baseline, i.e. when the child is
      between 4-6 months of age, and at 9, 12 and 18 months of age. At these time points the
      participants will come to the Paediatric Research Unit for measurements and sampling.

      Procedures The baseline visit and the 9mo. visits will take place at the Paediatric Research
      Unit at the Department of Clinical Sciences, Paediatrics, Umeå University Hospital (Figure).
      At ages 7, 8, 10, 11 and 13-17 mo. the research nurse or dietician will have a telephone
      follow-up with the participants checking adherence, possible study related problems, supply
      and consumption of study products and the symptoms registrations. At 12 and 18 mo. the
      participants will again come to the Paediatric Research Unit for samples. Also, the research
      nurse will do home visits for anthropometric measurements, TBW and the two videotaped tests,
      i.e. food acceptance test and the free play test.

      Informed consent and withdrawal A written Informed Consent from the subject's
      parents/caregiver is an inclusion criterion without which the subject cannot be included in
      the study. The participants may withdraw from the study at any time by withdrawing consent,
      through noncompliance or if the participant experiences adverse events requiring the
      participant to withdraw on advice of the research physician or by his/her own accord. If
      possible the reasons for withdrawal will be recorded. Participants that are withdrawn will
      not be replaced.

      D. Statistical analyses and ethical clearance Comparisons of differences in main outcomes
      between the ND and control groups will be the focus of the statistical analyses. The primary
      outcomes will be analysed according to the intention-to-treat principle when comparing the
      two study groups, but per protocol analyses will also be done. Both parametric and
      nonparametric tests will be used depending on the distribution of data. Possible effect
      modifiers and confounders will be included in the analyses as needed to explain group
      differences. Data on dietary intake will be converted to energy and nutrients through
      nutrient calculation software (Dietist NET, Kost och Näringsdata AB, Bromma, Sweden). The
      study has ethical clearance from the Regional Ethics committee, Umeå University (Dnr
      201436331M).
    

Intervention name(s): Systematic introduction of taste portions; Protein reduced complementary foods; Nordic diet
Intervention type(s): Other; Other; Other
Intervention description(s): A systematic introduction of plant foods from the Nordic diet; Specially prepared, protein-reduced, age-adjusted milk cereal drinks, baby cereals and baby milk, and commercially available baby foods in glass jars; Taste portions, homemade and industry manufactured main meals with a predominance of Nordic ingredients
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Nordic countries; Eating behavior; Human microbiome; Child nutrition; Metabolic profile; Body composition