The study design was a retrospective cohort study. All infants admitted to our neonatal intensive care unit (NICU) from January 2015 to December 2019 were included in the analysis. These infants had GA < 26 weeks at birth and reached the postmenstrual age (PMA) of ≥ 37 weeks. Study subjects consisted of 30 preterm infants, and 28 infants were examined. The other two infants died shortly after birth. One of the 28 infants was small for GA (SGA) with a birth weight and height of less than the 10% tile, and was excluded from the analysis of body weight change during hospitalization. The NICU databases were used as information sources: GA, body size (weight, height, head circumference) at birth, presence of SGA, age when the feeding targets (enteral feeds ≥ 100 ml/kg per day, ≥ 160 ml/kg per day) were achieved, body measurements (weight, height, head circumference) at 37 weeks PMA, the ratio of weight less than the 10% tile at 37 weeks PMA, early postnatal weight loss rate, and days to regain birthweight. We also assessed weight change from birth at 41 weeks PMA, short-term prognosis, complications of total parenteral nutrition (TPN), head circumference at 12 and 18 months, developmental quotient (DQ) at 2 years of age, and head circumference and weight at 3 years age. The 2-year-old DQ was assessed using the Enjoji’s development scale.
For complications associated with TPN, maximum measurements of blood urea nitrogen (BUN), direct bilirubin (d-bil) and bile acid were recorded from the results of regular blood sampling during hospitalization. Ammonia levels were recorded at 1 week after birth. The endpoint of short-term prognosis was necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA) treated with indomethacin and/or surgery, retinopathy of prematurity (ROP) treated with laser phototherapy, and intraventricular hemorrhage (IVH) grades III–IV. Necrotizing enterocolitis was defined using Bell’s classification stage 2 or more. The PDA was diagnosed clinically or with echocardiography and was considered clinically significant when it required medical treatment. The IVH was defined using Papile’s classification with ultrasonography. The ROP was treated with laser treatment if it had reached stage III of the international classification as diagnosed by an ophthalmologist. We also investigated the introduction rate of home oxygen therapy, home high-flow nasal canula therapy, home continuous positive airway pressure, tracheostomy, and home tube feeding at discharge.
The protocol for EAN at our facility was as follows: >3.0 g/kg/day amino acid (AA) solution along with a glucose infusion rate of 5.5 mg/kg/min using a 10% glucose solution was started in the first days after birth. At day 2 after birth, lipid emulsion was introduced at 1.0 g/kg/day and was increased every day to a maximum of 3.0 g/kg/day. Fifty mL TPN preparations contained 30 mL of AA (provided as Pleamin-P Injection, Fuso Pharmaceutical Industries, Osaka, Japan), 10 mL of 50% glucose solution, 1 ml of 10% sodium chloride solution, 1 mL dipotassium phosphate solution, and 8 mL distilled water. Additionally, a vitamin preparation (provided as MULTAMIN®ฎ FOR INJECTION, AY PHARMACEUTICALS, Tokyo, Japan), and a trace element preparation (provided as Elemenmic Injection, AY PHARMACEUTICALS. Tokyo, Japan) were added. The lipid emulsion (provided as Intralipos Injection 10%, Otsuka Pharmaceutical Factory, Tokyo, Japan) was administered in parallel from the side tube of the central catheter. Fluids were started at a rate of 80–100 ml/kg/day and increased to 150–160 ml/kg/day. For enteral nutrition, breast milk was used at first, and artificial milk was avoided as much as possible until day 5 after birth. The dose of TPN preparations were increased while replacing enteral nutrition with intravenous nutrition, and used in combination until full feeding was reached. Data analysis was divided into two groups, GA22–23 weeks and GA24–25 weeks. The Z score was calculated using the standard physique at birth by gestational age of Japanese. Additionally, body weight was measured daily until 41 weeks PMA, the Z score was calculated, the average value of each body weight was calculated, and the transition of body weight change was shown as data. The data of SGA was excluded.
Head circumference and height could not be calculated because weekly measurements were not taken. The data analysis was performed using the JMP software program, version 14 (SAS Institute, Cary, NC, USA). Data for two groups were compared using the Mann-Whitney U test and chi-square test. The level of significance was set at P < 0.05.