Incidence and two-year neurodevelopmental outcomes of small-for-gestational-age preterm infants: how do they relate to using different neonatal anthropometric charts?

BACKGROUND: The effect of different neonatal anthropometric charts on the incidence and neurodevelopmental outcomes at two years (Y) corrected age of small-for-gestational-age (SGA) preterm infants has still not been fully explored. METHODS: All preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks (W), born from Jan-2004 to Dec-2017 in the Marche region (Italy) were studied. Intergrowth-21st, Beeby, Fenton, and Bertino anthropometric charts were used to classify infants with a birth weight less than 10th centile as SGA. Disabilities and neurodevelopmental scores assessed by Bayley-III Test were recorded at the 2Y follow-up visit. RESULTS: One thousand one hundred forty-seven preterm infants were evaluated. The incidence of SGA was significantly different among the study charts (from 12.9 to 17.5%). Nine hundred and twenty-seven study infants were assessed for neurodevelopmental outcomes at 2Y corrected age. The incidence of SGA with moderate cognitive impairment (COG Score: 70-84) and mild neurodevelopmental disability (NDD) were significantly different between the Intergrowth-21st and Bertino charts (31.7% vs. 19.6%, P=0.042; 30.8 vs. 19.2%, P=0.036; respectively). A statistically significant difference in COG Score was found between SGA preterm infants overlapping in all study charts and those classified as SGA only by the Intergrowth-21st chart (89.1±15.7 vs. 99.2±19.8; P=0.038). CONCLUSIONS: In a large cohort of preterm infants with a GA between 24.0 and 31.6W, the incidence and neurodevelopmental outcomes at 2Y corrected age of SGAs were significantly different depending on the anthropometric charts. These differences, albeit small, should be considered both in clinical practice and trials on SGA preterm infants.

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.

Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

OBJECTIVES: To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS: We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%>10H) and the 24 months neurodevelopment. RESULTS: Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55%>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55%>10H were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS: NIRS<55%>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

Is intravenous fish oil associated with the neurodevelopment of extremely low birth weight preterm infants on parenteral nutrition?

BACKGROUND & AIMS: Preterm infants are at increased risk of long-term neurodevelopmental disabilities (NDD). Long chain n-3 fatty acids play a key role during the development of the central nervous system and some studies in preterm infants showed benefits of docosahexaenoic acid and arachidonic acid supplementation for visual and cognitive development. In recent years fish oil has been added to the fat blend of intravenous (IV) lipid emulsions (LE) but to date scanty data are available on neurodevelopmental outcome of preterm infants that received fish oil containing LE. We studied the effect of fish oil containing IV LE vs standard IV LE on neurodevelopment in a large cohort of preterm infants who received routine parenteral nutrition (PN) from birth. METHODS: We retrospectively reviewed the neurodevelopmental outcome of 477 preterm infants (birth weight (BW): 400-1249 g and gestational age (GA) at birth: 24+0 - 35+6 weeks (W)) admitted to our NICU between Oct-2008 and June-2017, who received routine PN with different LE, with and without fish oil (IV-FO vs CNTR). We compared neurodevelopment at 2 years corrected age by the Bayley III development scale and the incidence of NDD. RESULTS: Demographics, birth data and the incidence of the main clinical short-term outcomes of prematurity were similar in the two groups (IV-FO: n = 178, GA 197 ± 14 days, BW 931 ± 182 g; CNTR: n = 192, GA 198 ± 15 days, BW 944 ± 194 g). No differences were found in maternal demographics nor in parental education between the two groups. Cognitive score was not significantly different between IV-FO and CNTR (92 ± 15 vs 93 ± 13, p = 0.5). No differences were found in motor and language scores, and in the incidence of NDD in the two groups. CONCLUSIONS: Contrary to our hypothesis, the use of fish oil containing LE in a large cohort of preterm infants on routine PN did not result in better neurodevelopment. Large randomized controlled trials powered for neurodevelopment are needed to clarify the impact of the widely used fish oil containing LE on neurodevelopment of preterm infants.

Hypertriglyceridemia and lipid tolerance in preterm infants with a birth weight of less than 1250 g on routine parenteral nutrition.

OBJECTIVES: To study the association of hypertriglyceridemia and of lipid tolerance with clinical and nutritional data in preterm infants receiving routine parenteral nutrition. DESIGN: We retrospectively studied 672 preterm infants (gestational age <32 weeks) with birth weight <1250 g, consecutively admitted to our NICU, born between 2004 and 2018. Selected prenatal data and interventions, parenteral intakes and diseases were considered. Hypertriglyceridemia was defined as plasma triglycerides >250 mg⋅dL-1. Lipid tolerance was defined as the ratio of plasma triglycerides to the intravenous lipid intake at the time of sampling. Variables associated to hypertriglyceridemia and to lipid tolerance were identified by multiple logistic and linear regression analyses. RESULTS: Hypertriglyceridemia occurred in 200 preterm infants (30%), ranging from 67% at 23 weeks to 16% at 31 weeks' gestation. In 138 infants (69%) hypertriglyceridemia occurred at a lipid intake of 2.5 g⋅kg-1 or less. Lipid tolerance was reduced especially in infants of less than 28 weeks' gestation (14.3 ± 9.3 vs 18.8 ± 10.2, respectively, p < 0.001). Lipid tolerance was negatively associated with respiratory distress syndrome (OR = -1.14, p = 0.011), patent ductus arteriosus (OR = -1.73, p < 0.001), small for gestational age (OR = -2.96, p < 0.001), intraventricular haemorrhage (OR = -3.96, p < 0.001), late onset sepsis (OR = -8.56, p = 0.039). CONCLUSION: Preterm infants on routine parenteral nutrition were able to tolerate markedly lower intravenous lipid intakes than the recommended target values of current guidelines. Lipid tolerance was associated with some of the major complication of prematurity, possibly at risk of developing hypertriglyceridemia.

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.

Oxygen saturation to fraction of inspired oxygen ratio in preterm infants on routine parenteral nutrition with conventional or fish oil containing lipid emulsions.

INTRODUCTION: The benefits of intravenous (IV) fish oil (FO), as a source of n-3 long-chain polyunsaturated fatty acids, on lung growth in preterm infants, remain controversial. AIM: To evaluate if IV FO improves lung growth in small preterm infants on routine parenteral nutrition (PN). MATERIALS AND METHODS: We retrospectively reviewed prospectively collected data of preterm infants with a birth weight <1250 g who received routine PN from birth. We compared patients who received FO containing IV lipid emulsions with infants who received conventional emulsions (CNTR). The oxygen saturation (SpO2 ) to a fraction of inspired oxygen (FiO2 ) ratio (SFR) at 36 weeks (W) of gestation was chosen as the primary outcome variable to assess lung growth. RESULTS: Four hundred and seventy-seven infants were studied: 240 received IV FO and 237 CNTR. While exposure to antenatal glucocorticoids was higher in IV FO group than in CNTR (95 vs 90%, P = .04), there were no differences in birth data, enteral and parenteral nutrition intakes, ventilator supports and drug therapies. The incidence of the most common complications of prematurity at 36 W was not different (bronchopulmonary dysplasia was 27 vs 21% in IV FO vs CNTR infants, P = .1). Weight gain from birth to 36 W was marginally, but significantly, higher (+0.5 g/kg/d, P = .03) in IV FO group vs CNTR. SFR increased from 32 W to 36 W in all study patients (P < .001). IV FO infants had significantly lower SpO2 from 33 W to 35 W (P < .001) and lower (worse) SFR at 36 W (432 ± 57 vs 444 ± 51, P = .026) compared to CNTR. CONCLUSION: Contrary to our hypothesis, the use of FO containing IV lipid emulsions for the routine PN of the preterm infant did not improve lung growth compared to the infants who received conventional IV lipid emulsions.

Hypertriglyceridemia and Intravenous Lipid Titration During Routine Parenteral Nutrition in Small Preterm Infants.

OBJECTIVES: In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR). METHODS: We retrospectively reviewed data of preterm infants with a birth weight (BW) <1250 g consecutively admitted to our neonatal intensive care unit (2004-2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement >250 mg/dL during the first 10 days of life. Patients with and without HiTG were match-paired for BW and gestational age. RESULTS: A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty-six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non-protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2-year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different. CONCLUSIONS: Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non-protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels >250 mg/dL.

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.

Plasma Phytosterol Half-Life and Levels Are Increased in Very Low Birth Weight Preterm Infants with Parenteral Nutrition-Associated Cholestasis.

Parenteral nutrition-associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable-oil-based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half-life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty-seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half-lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 ±6.2 vs 11.8 ±3.0 days, p = 0.001; Stigma: 13.8 ±5.8 vs 9.4 ±3.4 days, p = 0.023; Sito: 15.3 ±5.0 vs 9.8 ±3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC.

Half-life of plasma phytosterols in very low birth weight preterm infants on routine parenteral nutrition with vegetable oil-based lipid emulsions.

BACKGROUND: Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE. METHODS: In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations-decay curves by using a single-compartment model. RESULTS: After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin. CONCLUSION: VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC. CLINICAL TRIAL REGISTRY: The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834).

Phytosterol Esterification is Markedly Decreased in Preterm Infants Receiving Routine Parenteral Nutrition.

Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500-1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography-mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free-CHO/Ester-CHO: 1.1 ± 0.7 vs. 0.6 ± 0.2; Free-PHY/Ester-PHY: 4.1 ± 2.6 vs. 1.3 ± 0.8; *P < 0.05). Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios of Term-PN (Free-CHO/Ester-CHO: 1.1 ± 0.4; Free-PHY/Ester-PHY: 2.9 ± 1.7) were not different from either Preterm-PN or from Adult-PN. Plasma Free-CHO/Ester-CHO and Free-PHY/Ester-PHY were unchanged after 24 h on fat-free PN both in Preterm-PN and in Adult-PN. Free-PHY/Ester-PHY did not correlate with phytosterol intake in Preterm-PN. Free-PHY/Ester-PHY of Preterm-PN was positively correlated with the Free-CHO/Ester-CHO and negatively correlated with gestational age and birth weight. In conclusion, PHY were esterified to a lesser extent than CHO in all study groups; the esterification was markedly decreased in Preterm-PN compared to Adult-PN. The clinical consequences of these findings warrant further investigations.

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.

Patent Ductus Arteriosus and Brain Volume.

BACKGROUND AND OBJECTIVES: A hemodynamically significant patent ductus arteriosus (PDA) can compromise perfusion and oxygenation of the preterm brain. Reports suggest that PDA is associated with increased mortality and morbidity. We hypothesize that long-standing low cerebral oxygenation due to PDA might affect brain volume at term equivalent age. METHODS: Observational study in 140 infants investigating the relationship between near-infrared spectroscopy-monitored cerebral oxygen saturation (rSco2) and MRI-assessed regional brain volume and maturation of the posterior limb of the internal capsule at term-equivalent age in 3 groups: those whose PDA closed with indomethacin, those who needed additional surgical closure, and matched controls. RESULTS: The surgery group had the lowest rSco2 values before closure (n = 35), 48% ± 9.7% (mean ± SD) as compared with the indomethacin (n = 35), 59% ± 10.4 (P < .001), and control groups (n = 70), 66% ± 6.9 (P < .001); the highest postnatal age before effective treatment; and the lowest volumes of most brain regions at term-equivalent age. Multiple linear regression analysis showed a significant effect of preductal closure rSco2 on cerebellar volume in this group. No differences were found in maturation of the posterior limb of the internal capsule. CONCLUSIONS: Long-standing suboptimal cerebral oxygenation due to a PDA may negatively influence brain growth, affecting neurodevelopmental outcome.

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.

Double blind exploratory study on de novo lipogenesis in preterm infants on parenteral nutrition with a lipid emulsion containing 10% fish oil.

BACKGROUND & AIMS: Provision of long chain polyunsaturated fatty acids (LCP) both of the omega-3 and omega-6 families is recommended for preterm infants (PI). Fish oil (FO) contains omega-3 and omega-6 LCP and it is incorporated in the fat blend of the new generation lipid emulsions (LE). Omega-3 LCP have been shown to reduce the expression of genes involved in lipogenesis, which could be important for several organs development. The aim of this study was to ascertain if the use of intravenous FO has an effect on lipogenesis in PI. METHODS: Forty PI were randomized to receive two LE: MSF (50:40:10 Medium Chain Triglycerides (MCT): Soybean oil (SO): FO) or MS (50:50 MCT:SO). We measured plasma lipids on day 7 and the fractional and absolute synthesis rates (FSR and ASR) of cholesterol and of selected fatty acids (FA) after (2)H2O body water labeling. RESULTS: Plasma phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) concentrations were all lower in MSF than in MS. In spite of lower plasma FC and CE concentrations, cholesterol biosynthesis was similar between the two study groups (FC: FSR 16.0 ± 1.4 vs 14.1  ± 1.1%/d, p = 0.74; ASR 6.8 ± 0.6 vs 7.1 ± 0.6 mg kg(-1) d(-1), p = 0.93; CE: FSR 3.6 ± 0.5 vs 4.2 ± 0.4%/d, p = 0.38; ASR: 3.3 ± 0.4 vs 4.4 ± 0.5 mg kg(-1) d(-1), p = 0.13, in MSF and MS respectively). FSR and ASR of selected FA were, or tended to be, lower in MSF than in MS. ASR of PL palmitate (4.0 ± 0.3 vs 4.8 ± 0.4 mg kg(-1) d(-1), p = 0.045), PL oleate (0.2 ± 0.04 vs 0.4 ± 0.05 mg kg(-1) d(-1), p = 0.02) and CE oleate (0.5 ± 0.1 vs 0.9 ± 0.1 mg kg(-1) d(-1), p = 0.03) were significantly lower in MSF than in MS. There were no differences in plasma TG FA biosynthesis. CONCLUSIONS: Cholesterol biosynthesis was not affected by 10% FO during neonatal parenteral nutrition. Ten percent FO caused a statistically significant reduction in the lipogenesis of selected FA and an overall tendency towards a reduced lipogenesis. The magnitude seems to be limited and the biological significance is unknown. Our data warrant follow-up studies in PI who receive intravenous FO, especially in those infants who receive larger doses than in the present study. Since this trial started in 2007, trial registration was not required.

Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial.

BACKGROUND & AIMS: Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. METHODS: Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. RESULTS: We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. CONCLUSIONS: The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008.

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.