Nutrition, growth, and allergic diseases among very preterm infants after hospital discharge.

The aims of this PhD thesis were: 1. Primarily to investigate the effect, of adding human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge, on growth until 1 year corrected age (CA) 2. Secondarily to describe breastfeeding rate and factors associated with breastfeeding among very preterm infants at hospital discharge. 3. To describe possible feeding-problems during the intervention-period, and allergic diseases during the first year of life, among very preterm infants related to their nutrition after hospital discharge. 4. To describe the content of macronutrients in human milk from mothers delivering very preterm. This PhD thesis is based on a prospective, randomized, and controlled interventional birth cohort study. A total of 633 very preterm infants with a gestational age (GA) ≤ 32 + 0 weeks were recruited consecutively from July 2004 until August 2008 of whom 157 were excluded due to diseases or circumstances influencing nutrition. Further 156 refused participation in the interventional part of the study, but data on breastfeeding, weight, and some epidemiological data until discharge were available. Results on breastfeeding rate at discharge were therefore based on data from 478 infants, and parents of 320 infants accepted participation in the intervention study. Of these 320 infants, 207 were exclusively breastfed and they were shortly before hospital discharge randomized to either breastfeeding without (group A) or with fortification (group B) until 4 months CA. Infants (n = 113) who were bottle-fed at discharge (group C) were given a preterm formula (PF) until 4 months CA. Infants were examined at the outpatient clinics at term, and at 2, 4, 6, and 12 months CA, where parameters on growth, allergic diseases, possible feeding problems, blood-samples, and milk samples were obtained. Data on duration of exclusively breastfeeding and time of introduction to formula and/or complementary food were also recorded. Among the 478 infants 60% (n = 285) were exclusively breastfed, 35% (n = 167) were exclusively bottle-fed, and 5% (n=26) were both breast- and bottle-fed at discharge. Compared to mothers in lower social groups and mothers who smoked, mothers in higher social groups and "non-smokers" were significantly (p = 0.000 and p = 0.003 respectively) more often breastfeeding their very preterm infants at discharge. Single birth infants tended more often to be breastfed (p = 0.09). Infant age at discharge and duration of hospitalization did not influence breastfeeding at discharge. Increase in weight Z-score from birth to discharge was largest in the bottle-fed group compared to the breastfed group (p = 0.000), probably due to feeding practice the last week(s) of hospitalization. In the intervention study, 207 exclusively breastfed very preterm infants were randomized to group A (n = 102) and B (n = 105) respectively. The duration of breastfeeding was not influenced by fortification of mother's milk after hospital discharge. There was no significant difference on growth comparing group A and B at 12 months CA. Both boys and girls in group C achieved catch-up in weight and length earlier as compared to group A and B. Per protocol (PP) analysis showed that girls, but not boys, were longer and had a larger head circumference but were not heavier in group B (n = 51) compared to group A (n = 73) at 2 and 4 months CA (p<0.05). Protein-concentration in mothers' milk declined significantly from 2 weeks (1.8 g/100 ml) to 6 weeks after birth (1.4 g/100 ml) and declined further to 1.2 g/100 ml 12 weeks after birth. The incidence and the prevalence at 12 months CA of recurrent wheezing was 39.2% and 32.7% respectively, while atopic dermatitis was 18.0% and 12.1% respectively. Predisposition to allergic disease increased the risk of developing atopic dermatitis (p = 0.04) (OR 2.6 (95% CI 1.0-6.4)), and the risk of developing recurrent wheezing (p = 0.02) (OR 2.7 (95% CI 1.2-6.3)). Boys had an increased risk of developing recurrent wheezing (p = 0.003) (OR 3.1 (95% CI 1.5-6.5)). In conclusion breastfeeding can successfully be established in very preterm infants. Fortification of human milk after hospital discharge while breastfeeding was possible without influencing the duration of breastfeeding. Fortification in the amount given in this study did, however, not affect growth significantly at 1 year of age. An increased amount of protein was correlated with increased BUN-values indicating a better growth potential. Fortification of mother's milk or preterm formula was not associated with an increased risk of developing allergic diseases. Future follow-up of this cohort investigating e.g. growth, allergic diseases, and neuropsychological development is planned at 6 years of age. The definition of optimal growth and nutrition of preterm infants is though still a question for debate and further investigations are needed.