Early postnatal weight loss does not affect the 2-year neurodevelopment in preterm infants of less than 32 weeks.

AIM: It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2-year corrected age in preterm infants. METHODS: We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.Salesi Children's Hospital, Ancona, Italy, between 1 January 2006 and 31 December 2019. Infants with PWL greater than or equal to 10% (PWL ≥ 10%) were compared with those with PWL of less than 10% (PWL < 10%). A matched cohort analysis was also performed using gestational age and birth weight as matching variables. RESULTS: We analysed 812 infants: 471 (58%) PWL ≥ 10% and 341 (42%) PWL < 10%. A subgroup of 247 PWL ≥ 10% was closely match-paired with 247 PWL < 10% infants. There were no differences in amino acid and energy intakes from birth to day 14 of life and from birth to 36 weeks. Although at 36 weeks, body weight and total length were lower in PWL ≥ 10% than PWL < 10%, anthropometry and neurodevelopment at 2 years were similar between groups. CONCLUSION: Given similar amino acid and energy intakes on PWL ≥ 10% and PWL < 10% preterm infants of less than 32 + 0 weeks/days, PWL does not affect 2-year neurodevelopment.

Which birth weight threshold to start parenteral nutrition? A single center experience.

OBJECTIVES: To analyze the need for parenteral nutrition (PN) in infants with a birth weight (BW) between 1250 and 1499 g. METHODS: Retrospective evaluation of clinical, nutritional, growth and neurodevelopmental data of infants with a BW between 1250 and 1499 g consecutively admitted to our institution between 2004 and 2020. RESULTS: Of the 503 infants admitted during the study period, 130 (26%) received PN: in 97 (19%) PN was medically indicated, while in 33 (7%) there was no clear indication. Patients who received medically indicated PN were younger, smaller, and sicker than the 373 infants who were managed with enteral nutrition, and their weight gain was lower (14.6 ± 4.1 vs 16.9 ± 4.2 g∙kg-1 ∙ d-1, p = 0.000). Body size at 36 weeks and 2-year anthropometry and neurodevelopment of the infants managed with enteral nutrition were not different from our reference values. CONCLUSIONS: After lowering the BW threshold for bridging PN from 1500 to 1250 g, we found that PN was started in only 20% of infants with a BW between 1250 and 1500 g. Withholding PN if not medically indicated did not result neither in growth faltering nor in reduced neurodevelopment.

Blood urea in preterm infants on routine parenteral nutrition: A multiple linear regression analysis.

BACKGROUND: Blood urea is considered a marker of amino acid utilization in preterm infants on routine parenteral nutrition. However, the association between blood urea and intravenous amino acid intake remains debated. AIMS: To evaluate the association between blood urea and both nutrition and clinical data, in a large cohort of preterm infants. METHODS: Consecutively admitted preterm infants with a gestational age of less than 32 weeks and a birth weight lower than 1250 g on routine parenteral nutrition from the first hour of life were studied. Clinical and nutrition data collected hourly during the hospitalization were used in multiple linear regression analysis. RESULTS: We studied 674 patients and 1863 blood urea determinations. Blood urea concentration was positively associated with blood creatinine concentration, intravenous amino acid intake, patent ductus arteriosus and respiratory distress syndrome, and negatively associated with intravenous non-protein energy intakes, daily weight change, gestational age, being small for gestational age, antenatal steroids therapy and reverse flow in the umbilical artery (p < 0.001; R = 0.7). CONCLUSIONS: From a nutrition perspective, in our large cohort of small preterm infants blood urea was positively correlated with intravenous amino acid intake and negatively correlated with intravenous non-protein energy intake. This is in line with current knowledge in human physiology and suggest that a reduction of intravenous amino acid intake based on blood urea concentrations was justified.

Does intravenous fish oil affect the growth of extremely low birth weight preterm infants on parenteral nutrition?

BACKGROUND & AIMS: Long chain n-3 fatty acids (n-3 LCPUFA) play a pivotal role during central nervous system development and the provision of docosahexaenoic acid (DHA) is recommended for the preterm infant. However, there are concerns that oral fish oil, which is a good source of DHA, may adversely affect growth of preterm infants, as it decreases arachidonic acid (ARA). It has been about ten years since fish oil was added to the fat blend of intravenous (IV) lipid emulsions (LE) but information on growth and other clinical outcomes of preterm infants is still scarce. We studied the effect of fish oil containing IV LE vs standard IV LE on growth in a large cohort of preterm infants who received routine parenteral nutrition (PN). METHODS: We retrospectively reviewed growth data of 546 preterm infants with a birth weight (BW) < 1250 g consecutively admitted to our NICU between Oct-2008 and Jun-2017 who received PN starting from the first day of life. Individual patients received only one of 5 commercially available IV LE. For the purpose of this study we grouped the patients who received the fish oil containing LE (IV-FO) and those who received conventional LE (CNTR). We compared PN and enteral nutrition (EN) intakes, and growth from birth to 36+0 weeks post-menstrual age (W PMA). RESULTS: Demographics, birth data and the incidence of the main complications of prematurity were similar between the two groups (IV-FO: n = 240, Gestational age (GA) 197 ± 16 d, BW 942 ± 181 g; CNTR: n = 237, GA 199 ± 17 d, BW 960 ± 197 g). No difference was found in PN and EN energy and macronutrient intakes from birth to 36+0W PMA, as well as in the proportion of human milk to infant milk formula. Weight gain from the regained BW to 36+0W PMA was slightly but significantly higher in IV-FO group: 17.3 ± 2.8 and 16.8 ± 2.7 g∙kg-1∙d-1, IV-FO and CNTR respectively (p = 0.03). There was no difference in length gain and head growth nor in body size at 36+0W PMA between the two groups. CONCLUSIONS: The use of IV fish oil did not negatively affect weight gain in a cohort of preterm infants. Large randomized controlled trials are needed to assess the effect of IV fish oil on the complication of prematurity and on selected domains of infant development.

Amino Acid Intake in Preterm Infants.

A large proportion of extremely low-birth-weight infants requires parenteral nutrition for variable lengths of time. Amino acids are the key ingredients of parenteral nutrition. The goal of appropriate amino acid administration is to promote anabolism and normal cellular development in order to limit the incidence of postnatal growth restriction, which is associated with neurodevelopmental delays. The benefits of early amino acid commencement soon after birth are compelling, especially on nitrogen balance, while long-term outcome studies are lacking. Amino acid administration at 2.5 g/kg per day has been shown to be superior to lower intakes; however, the benefits of intakes above 2.5 g/kg per day remain controversial.

One Extra Gram of Protein to Preterm Infants From Birth to 1800 g: A Single-Blinded Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the effect on growth and neurodevelopment of increasing amino acid (AA) during parenteral nutrition and protein intake during enteral nutrition in extremely low birth-weight infants starting from birth to day of reaching 1800 g body weight. METHODS: We randomized preterm infants with birth weight 500 to 1249 g either to a high AA/protein intake (HiP [high protein]: parenteral nutrition = 3.5 AA, enteral nutrition = 4.6 protein g ·â€Škg ·â€Šday) or to a standard of care group (StP [standard protein]: parenteral nutrition = 2.5 AA, enteral nutrition = 3.6 protein g ·â€Škg ·â€Šday). The primary outcome was weight gain from birth to 1800 g. RESULTS: TWO:: hundred twenty-six patients were screened, 164 completed the study and were analyzed (82 StP and 82 HiP). Cumulative AA/protein intake from birth to 1800 g was 178 ±â€Š42 versus 223 ±â€Š45 g/kg in the StP versus HiP group respectively, P < 0.0001.Blood urea was higher in HiP than in StP group both during parenteral and enteral nutrition (P = 0.004).Weight gain from birth to 1800 g was 12.3 ±â€Š1.6 in StP and 12.6 ±â€Š1.7 g ·â€Škg ·â€Šday in HiP group (P = 0.294). We found no difference in any growth parameters neither during hospital stay nor at 2 years corrected age. Bayley III score at 24 months corrected age was 93.8 ±â€Š12.9 in StP group and 94.0 ±â€Š13.9 in the HiP group, P = 0.92. CONCLUSIONS: Increasing AA/protein intake both during parenteral and enteral nutrition does not improve growth and neurodevelopment of small preterm infants 500 to 1249 g birth weight.

Targeting 2.5 versus 4 g/kg/day of amino acids for extremely low birth weight infants: a randomized clinical trial.

OBJECTIVE: To compare the effect of 2.5 vs 4 g/kg/d of amino acid (AA) in parenteral nutrition of extremely low birth weight infants on metabolic tolerance, short-term growth, and neurodevelopment. STUDY DESIGN: One hundred thirty-one infants with birth weight between 500 and 1249 g were randomized to 2.5 (standard AA [SAA] group) or 4 (high AA [HAA] group) g/kg/d AA intake, with equal nonprotein energy. The primary outcome was body size at 36 weeks. RESULTS: One hundred thirty-one patients were randomized and 114 analyzed (58 SAA group and 56 HAA group). Study groups had similar demographics and clinical characteristics. Elevated blood urea (BU >70 mg/dL = BU nitrogen >32.6 mg/dL) occurred in 24% vs 59% (P = .000) and hyperglycemia (>175 mg/dL) in 34% vs 11% (P = .003) of the SAA and HAA patients, respectively. Body weight, length, and head circumference at 36 weeks and 2 years were similar between groups. Bayley Scales of Infant and Toddler Development, Third Edition score was 94 ± 13 in the SAA group and 97 ± 15 in the HAA group (P = .35). CONCLUSIONS: The HAA group had higher BU levels and better glucose control. An extra 8 g/kg of AA over the first 10 days of life did not improve growth and neurodevelopment.

Parenteral nutrition of preterm infants with a lipid emulsion containing 10% fish oil: effect on plasma lipids and long-chain polyunsaturated fatty acids.

OBJECTIVE: To compare plasma lipids in preterm infants given a new lipid emulsion containing 10% fish oil, 50% medium-chain triacylglycerols, and 40% soybean oil, compared with a standard preparation containing 50:50 medium-chain triacylglycerols: soybean oil. STUDY DESIGN: Preterm infants weighing <1250 g at birth (n=47) were randomly assigned to receive parenteral nutrition with a fish oil lipid (n=23) or soybean oil (n=24). Plasma lipid classes and plasma and red blood cell fatty acids were determined by gas chromatography in cord blood and on postnatal days 7 and 14. RESULTS: On day 7, the infants receiving fish oil lipid had significantly lower plasma phospholipids, cholesterol esters, and free cholesterol but similar triglyceride concentrations. They also had significantly higher phospholipid docosahexaenoic acid (2.77 ± 0.08 versus 2.46 ± 0.01 mol%, P<.01) and eicosapentaenoic acid (1.58 ± 0.01 versus 0.25 ± 0.01 mol%, P<.01) as well as lower arachidonic acid (10.64 ± 0.29 versus 11.93 ± 0.29 mol%, P<.01) compared with those receiving soybean oil. Similar differences were found in red blood cells. CONCLUSIONS: The fish oil lipid emulsion was well tolerated, and infants receiving fish oil had lower plasma lipids and improved fatty acids status. The effect of these changes on inflammation, growth, and neurodevelopment should be explored.

Pharmacokinetics and clinical predictors of surfactant redosing in respiratory distress syndrome.

RATIONALE: Limited data are available on predictors for surfactant retreatment in preterm infants with respiratory distress syndrome (RDS). OBJECTIVE: To study the pharmacokinetics of exogenous surfactant and the clinical parameters associated with surfactant redosing. METHODS: Exogenous surfactant pharmacokinetics was studied in 125 preterm infants (birth weight 997 ± 432 g; gestational age 28.0 ± 2.6 weeks) with moderate to severe RDS requiring mechanical ventilation. Clinical and respiratory parameters were recorded hourly, and surfactant disaturated-phosphatidylcholine (DSPC) half-life, pool size, and endogenous synthesis were calculated by stable isotope tracing of surfactant DSPC isolated from serial tracheal aspirates. Univariate and multiple logistic regression were used to study the effects of clinical and surfactant kinetic variables on the need for redosing. RESULTS: Fifty-three infants (42.4%) received one dose, 51 (40.8%) two doses, and 21 (16.8%) three doses. Median (interquartile range, IQR) DSPC half-life was 21 (13-39), 11 (7-17), and 10 (7-16) h after the first, second, and third dose, respectively (p = 0.07). Univariate analysis showed a significantly shorter DSPC half-life in infants requiring more surfactant doses. On logistic analysis, risk of redosing was higher with lower birth weight, worse radiological score, shorter DSPC half-life, and surfactant dose of 100 mg/kg, whilst it was lower with elective high-frequency ventilation at time of intubation, instead of conventional ventilation. CONCLUSIONS: When optimizing surfactant replacement therapy and its cost-benefit ratio, pharmacokinetics and clinical variables associated with need of redosing should be taken into account.