Preterm infants (gestational age between 189 and 258 days) with a birth weight (BW) greater than 1250 grams will be randomized to personalized-parenteral nutrition (P-PN) or standardized-parenteral nutrition (S-PN). The aim of the study is to evaluate the effect of S-PN versus P-PN on growth of preterm infants with BW\>1250 grams.
Parenteral nutrition (PN) is a crucial part of the clinical care of preterm infants. Traditionally different components of PN are prescribed individually considering requirements of an individual infant (P-PN). Recently, standardized PN formulations (S-PN) for preterm infants have been assessed and may have advantages including a better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bags that provides total nutrient admixture for infants may have the additional advantage of decreased risk of contamination and ease of administration. The proposed intervention and hypothesis: The investigators propose a multi-centered Phase IV RCT to compare S-PN versus P-PN, that is the usual care for preterm infants with a birth weight \>1250 grams requiring PN in the intensive care units involved in the study. The investigators hypothesize that weight gain during PN of preterm infants with a BW greater than 1250 grams who received S-PN is not statically inferior (\< 2g/kg/d) to that of infants who received P-PN (Non-inferiority study). Study design: Preterm infants (gestational age between 189 and 258 days) with a BW greater than 1250 grams will be enrolled during hospitalization after the informed consent is drawn from parents or legal guardians. All infants will undergo a physical examination and the need of PN will be judged by the caring physician according to predefined criteria. Infants requiring PN will be divided into 3 clinical groups: * Group A or EARLY HIGH-RISK INFANTS: these infants present in rather severe conditions at birth or soon after birth which make enteral nutrition (EN) impossible or non-desirable. In this group of infants, the investigators will include patients with Perinatal asphyxia, Perinatal shock (Cardiovascular or Septic), GI malformations, Severe Intra-uterine growth retardation (IUGR) with markedly abnormal prenatal doppler, and Miscellanea. These infants will have a central venous access soon after birth. * Group B or INSUFFICIENT EN INTAKE: these Infants are in rather stable conditions after birth, however these infants may exhibit gastrointestinal (GI) intolerance of any origin. These patients will be randomized after 72 hours of life if the mean EN volume of the first 72-hrs of life will be less than 30 ml/kg/d or if EN intake on the third day will be less than 45 ml/kg/d. In this category, the investigators will include also those infants who will have their EN intake reduced below 30 ml/kg for 3 consecutive days (usually from day 3 through day 6) because of PDA treatment. These infants will have a central venous access inserted on the 3rd or 4th day of life if not already in place. * Group C or LATE SICKNESS: these are the infants that experience a major sickness after a variable period of good gastrointestinal tolerance. In this group, the investigators will have infants with Necrotizing Enterocolitis (NEC), Severe Sepsis with abdominal distension and poor peristalsis, Septic Shock, or other severe unexpected conditions such as volvulus etc. These infants will also have a central venous access. Study infants within each clinical group will be divided into 2 blocks on the basis of their BW: 1250-1750 g (Block A) e \>1750 g (Block B). Infants of each study group will be then randomly assigned to P-PN or S-PN (Intervention-arm). The study PN bags will be used until the study infants will not be able to tolerate 135 ml/kg/d enterally (range: 120-160 ml/kg/d according to the local practice) or until day 28 of PN (after the 28th day of PN, patients will receive PN according to the normal clinical practice).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
150
NUMETA G13%E 300 mL is a triple-chamber (lipid emulsion, amino acids solution with electrolytes, and glucose solution), ready-to-use parenteral nutrition product available to treat preterm infants (less than 37 weeks gestational age).
Intravenous glucose will be "dextrose 50%", amino acids (AA) will be "Primene®" and lipids (FAT) will be "Clinoleic®". Parenteral nutrition bags will be prepared by the hospital pharmacy according to the prescription of the attending neonatologist.
Ospedali Riuniti Ancona
Ancona, Italy
RECRUITINGAzienda Ospedaliera di Padova
Padova, Italy
RECRUITINGHospital Universitario La Paz
Madrid, Spain
RECRUITINGWEIGHT CHANGE
Daily weight change (g/kg/d) during parenteral nutrition (PN)
Time frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 7 days of PN will be required to calculate weight gain during PN.
MUSCLE ULTRASOUND (optional)
Ultrasound measurement of mid thigh and mid arm muscle thickness (cm).
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
ADIPOSE TISSUE ULTRASOUND (optional)
Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm).
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
BONE ULTRASOUND (optional)
Metacarpus speed of sound (m/s) and metacarpus bone transmission time (ms).
Time frame: At the start of PN, after 7, 14 and 28 days (+-1 d).
WEIGHT
Weight measured by a digital infant scale (grams)
Time frame: Daily up to 42 weeks of post menstrual age or discharge if it comes first.
TOTAL BODY LENGTH
Total body length measured by a neonatal stadiometer (cm)
Time frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
HEAD CIRCUMFERENCE
Head circumference measured by a flexible non-stretchable tape (cm)
Time frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
GLUCIDE TOLERANCE
Blood glycemia (mg/dl).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
AMINO ACID TOLERANCE
Plasma and urinary urea concentrations (mg/dl).
Time frame: At the start of PN, at PN day 7 (+-1 d) and 14 (+-1 d), and then every 2 weeks until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
TRIGLYCERIDE CONCENTRATION
Plasma triglycerides (TG; mg/dl).
Time frame: At PN day 3 (+-1 d) and 7(+-1 d), and then every 7 days (+-1 d) until the stop of PN (endpoint: PN day 28 if PN duration >28 days).
FATTY ACID CONCENTRATION (optional)
Plasma fatty acid concentration (FA; mg/dl).
Time frame: At PN day 7 (+-1 d).
DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional)
Urinary dicarboxylic acids (DCA; mmol/mol creatinine) and hydroxyl fatty acids (H-FA; mmol/mol creatinine).
Time frame: At PN day 7 (+-1 d).
ELECTROLYTE CONCENTRATION
Hemogasanalysis (Na+, mmol/l; K+, mmol/l; Ca2+, mg/dl; Cl-, mmol/l) and SBE (standard base excess, mmol/L)
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM
Episodes of Hyper/Hypo Natremia, -KaIemia, -Chloremia, -Phosphatemia, -Calcemia, and -Parathyroidism (number).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
METABOLIC ACIDOSIS
SBE \< -7.5 mmol/L.
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS
Plasma and urinary calcium and phosphorus concentrations (mg/dl).
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS
Plasma alkaline phosphatase (ALP; UI/L), aspartate transaminase (AST; UI/L), alanine transaminase (ALT; UI/L), and gamma-glutamyl transpeptidase (GGT, UI/L).
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION-2: PTH CONCENTRATIONS
Plasma parathormone concentrations (PTH; pg/ml).
Time frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN.
BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional)
Urinary pyridinoline crosslinks of collagen (Pyd; nmol/L), serum carboxyterminal propeptide of type I procollagen (PICP; ng/mL) and serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP; ng/mL)
Time frame: At the start of PN and at PN day 28 (+-1 d) (endpoint).
BILIRUBIN CONCENTRATION
Plasma bilirubin (total and conjugated; mg/dl)
Time frame: At PN day 7 (+-1 d). An additional measurement will be performed at PN day 14 (+-1 d) in case of PN duration >14 days.
MORBIDITY - 1
The incidence of the main complication of prematurity (intraventricular hemorrhage of 3° and 4° grade; Periventricular leukomalacia; Patent ductus arteriosus; Retinopathy of Prematurity; Bronchopulmonary dysplasia and Sepsis).
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
MORBIDITY - 2
The incidence of Cholestasis and Renal and Hepatic Insufficiency.
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE
Death before 42 weeks post menstrual age (number).
Time frame: At 42 weeks of post menstrual age or discharge if it comes first.
MORTALITY DURING PARENTERAL NUTRITION
Death during PN (number).
Time frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
ENTERAL NUTRITION INTAKES
Enteral nutrition intakes (ml/kg).
Time frame: Daily from the start of PN to day 28 of life.
PARENTERAL NUTRITION INTAKES: AMINO ACIDS
Intravenous amino acid intakes (g/kg).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: LIPIDS
Intravenous lipid intakes (g/kg).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION INTAKES: GLUCOSE
Intravenous glucose intakes (g/kg).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
PARENTERAL NUTRITION DURATION
PN duration (days).
Time frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days).
MECHANICAL VENTILATION
Mechanical ventilation duration and oxygen therapy duration (days).
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
DRUG THERAPIES
Drug therapy duration (hours).
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
PHARMACOECONOMICS
Healthcare costs (euro).
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.
METABOLIC COMPLICATIONS
Number of hypertriglyceridemic episodes (plasma triglycerides\>265mg/dL), hyperglycemic and hypoglycemic episodes (blood glycaemia\>175 mg/dL and \<40 mg/dL, respectively) and elevated urea (blood urea\>100 mg/dL).
Time frame: Up to 42 weeks of post menstrual age or discharge if it comes first.