Feeding late and moderately preterm infants

INTERVENTION: Please note that infants are first recruited to an observational cohort. From within this cohort infants who are eligible will be enrolled to an RCT. Outcomes are the same for both groups. Infants will be enrolled and randomised using an online randomisation programme www.sealedenvelope.com. Infants are assigned to a product code (A, B, C or D) using a minimisation process (with a 30% chance of simple random allocation) and will use two stratification factors. All members of the research team are blinded to treatment allocation. Stratification is applied for: 1. Multiple births (single vs multiple birth) 2. Gestational age (32‐33 vs 34‐36 weeks) In case of multiple births, the first eligible sibling is randomised according to the stratification factors above and if applicable, the other sibling(s) will be automatically provided the same treatment code. Infants will be allocated of two study formula milks (control and intervention) which will be fed on demand until 6 months corrected age (total duration 6 – 7 months). Infants will be reviewed by telephone and at pre‐planned clinic visits. After 6 months corrected age the study intervention will stop and infants will be advised on feeding methods according to standard guidelines. Infants will be followed in clinic until 2 years corrected age. The two milk formula meet international recommendations for nutrient intakes in infancy and contain similar amounts of macro‐ and micro‐nutrients. They differ only in the structure of the lipid droplet which is larger in the intervention formula. CONDITION: Specialty: Children, Primary sub‐specialty: Neonatal; UKCRC code/ Disease: Reproductive Health and Childbirth/ Disorders related to length of gestation and fetal growth ; Neonatal Diseases PRIMARY OUTCOME: Daily weight gain from randomisation until 3 months corrected age. Weight measured using standard weighing scales at baseline, discharge, term equivalent age (TEA), 3,6,12 and 24 months corrected age SECONDARY OUTCOME: 1. Growth (weight, length and head circumference) from term equivalent age (TEA) until 3 months. Length and head circumference are measured using standard linear length boards and head circumference using non‐stretchable tape measures at term and 3 months corrected age; 2. Body composition measured by Dual X‐Ray Absorptiometry (DEXA) before/at term and 3 months corrected age. DEXA will provide lean body mass, total body fat mass, % fat and lean body mass, fat mass index, fat free mass index, bone mineral density, bone mineral content, ulna and lower leg length; 3. Anthropometry: weight, length, head, mid‐upper arm and mid‐thigh circumference (using tapes) at baseline, discharge, term equivalent age (TEA), 3,6,12 and 24 months; 4. Skinfold thicknesses using Harpenden calipers: triceps, biceps, supra‐iliac, subscapular at baseline, discharge, term equivalent age (TEA), 3,6,12 and 24 months; 5. Arm muscle area, arm fat area and arm fat % calculated from mid‐upper arm circumference and triceps skinfolds; 6. WHO Z‐scores of anthropometric parameters at baseline, discharge, term equivalent age (TEA), 3, 6, 12 and 24 months: ; 6.1. Weight‐for‐age z scores ; 6.2. Weight‐for‐length z scores; 6.3. Length‐for‐age z scores ; 6.4. Body Mass Index‐for‐age (BMI‐for‐age) z scores. BMI is automatically calculated from weight divided by height squared [kg/m2] ; 6.5. Head circumference‐for‐age z scores ; 6.6. Mid‐upper arm circumference‐for‐age z scores (from 3 months corrected age onwards); 6.7. Skinfold‐for‐age z‐scores (subscapular, triceps; from 3 months corrected age onwards); 7. Gain in above mentioned growth and body composition parameters and (when applicable) their z‐scores during the study, including at least the following time intervals: randomization/term to 3 months corrected age, randomization/term to 6 months corrected age, 6 to 12 months of corrected age and 12 to 24 months corrected age; 8. Number, type and severity of (serious) adverse events up to 12 months of corrected age; 9. Number, type and severity of serious adverse events which could potentially be related to the use of study product, and the corresponding medication used, during the follow‐up period (until 24 months of corrected age); 10. Use of medication and nutritional supplements up to 12 months corrected age at baseline, discharge, term equivalent age (TEA), 3, 6, 12 and 24 months; 11. Gastrointestinal tolerance parameters at discharge, term equivalent age (TEA), 3, and 6 months corrected age via parental recall, including: ; 11.1. Occurrence and severity of gastrointestinal symptoms (stooling, reflux, spitting up/vomiting, flatulence, crying and/or fussiness, diarrhea), using a 5‐point scale to indicate severity; 11.2. Stool characteristics recording by parental recall using questions that are already provided together with educational material in an information booklet ; 11.3. Stool frequency (number of stools); 11.4. Stool consistency, scored on a 4‐point scale using pictures to indicate score: watery (=1), soft (=2), formed (=3) or hard (=4); 12. The Parent Report of Children’s Abilities‐Revised (PARCA‐R) questionnaire scores are recorded to assess cognitive and language development at 24 months corrected age; 13. Baby eating behaviour questionnaire outcomes at term and 3 months; 14. Infant’s eating behaviour (Baby Eating Behaviour Questionnaire: BEBQ); 15. Infant’s bottle‐emptying behaviour is assessed by asking the main caregiver to answer 2 questions relating to bottle emptying on a 5‐point scale [never (= 1) / rarely (= 2) / sometimes (= 3) / most of the time (=4) / always (=5)]: “How often does your baby drink all of his or her bottle of formula?” and “How often does your baby drink all of his or her cup or bottle of pumped milk?”; 16. Questions to record age at introduction of complementary feeding, age at introduction of infant formula (breastfed reference) and duration of (any) breastfeeding will be asked at term, 3 and 6 months; 17. Food frequency questionnaires to assess dietary intake at 6 and 12 months of corrected age; 18. Child eating behaviour questionnaire at 12 and 24 months of age INCLUSION CRITERIA: 1. Healthy moderate to late preterm infants (gestational age = 32 and = 36 6/7 weeks) 2. Age at inclusion = term equivalent age 3. Birth weight between 1.25‐2.5 kg 4. Infants who are predominantly formula fed (max. 1 breastfeeding per day) using a standard term infant formula 5. Written informed consent from parent(s) and/or legal guardian, aged = 18 years, to be enrolled into a randomised trial