Early Higher Intravenous Lipid Intake in VLBW Infants

NCT ID: NCT03594474

Last Updated: 2021-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-15
• Study Completion Date: 2019-10-19

Brief Summary

Provision of high and early fat intake may help to reduce the amount of postnatal weight loss in Very Low Birth Weight Infants. It may also help utilize the high amount of protein that is currently recommended to these premature babies. Also, we expect babies who get this appropriate intake to regain their birth weight earlier than others who are on slow fat increase regimen.

Detailed Description

The recommendation of the Pediatric Societies of North America and Europe is that postnatal growth of preterm infants matches the in-utero growth rates of fetuses that remain in utero until full-term. Despite this long-standing recommendation, approximately 43% to 97% of very low birth weight (VLBW, less than 1500 g) infants grow slower than the estimated fetal growth velocity. This slow postnatal growth usually results in extra-uterine growth restriction (EUGR), defined as having a measured growth parameter (weight, length, or head circumference) that is less than 10th percentile of intrauterine growth expectation based on estimated postmenstrual age (PMA) in premature neonates at the time of hospital discharge.4 EUGR is associated with major morbidities such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and impaired neurodevelopment.

Although the etiology of EUGR is multifactorial, inadequate nutrition plays a pivotal role. There are three critical stages of nutrition support in VLBW infants: (1) acute stage during the first 1-3 weeks after birth when infants are on parenteral nutrition, (2) intermediate period when infants are slowly advanced to full enteral nutrition (growing care stage), and (3) the post-discharge stage. Failure to provide adequate nutrition in the acute stage result in cumulative energy and protein deficits that is difficult to reverse in the second stage. Inadequate early postnatal nutrition results in excessive weight loss that cannot be explained by the physiologic contraction of body water alone. The regain of birth weight may need two to three weeks or even longer in preterm infants with excessive postnatal weight loss.

Newborn infants born at term normally lose 5-10% of their body weight in the first week of life due to contraction of extracellular water compartment. The proportion of weight loss is significantly higher in VLBW infants. Increased insensible water loss is widely considered as the main cause for additional weight loss in this population. Nevertheless, studies identified low energy intake to be a key driver to excessive weight loss. In fact, an earlier study showed that significant postnatal weight loss occurs mainly in infants whose energy intake is inadequate. A more recent epidemiologic study demonstrated similar postnatal growth trajectories with a minimal crossing of percentiles after the initial weight loss regardless of gestational age at birth. The growth trajectories for infants in that study had similar slopes and growth rates which indicate that proportion of postnatal weight loss is a lead cause for EUGR at discharge. Therefore, we speculate that decreasing the maximum percentage of initial weight loss in the acute stage would keep the preterm infant on a higher growth trajectory that is enough to reduce the incidence of EUGR.

Current fat provision regimen for preterm infants include starting parenteral lipid at 12-24 hours of age with 0.5-1 g/kg per day and advancing by 0.5 g/kg/day until reaching 3 g/kg per day. Using early (within one hour of birth) and higher (start at 2 g/kg per day and advance to 3g/kg per day once total fluid intake is increased to 80 ml/kg/day) parenteral fat intake could reduce the cumulative caloric deficit in the acute stage. Because of high-density energy in fat, higher parenteral fat intake will reduce the early energy deficit and enhance protein accretion. The first 2-3 weeks of life offer a critical window to limit postnatal nutritional and energy deficits. Recent study showed that higher energy and fat intakes during the first 2 weeks after birth are associated with a lower incidence of brain lesions and dysmaturation at term equivalent age in preterm neonates.

To date, studies of "early aggressive nutrition" in preterm infants have mainly focused on high protein intake to prevent protein catabolism. Nevertheless, provision of high protein intake without enough energy is unlikely to significantly reduce the early loss of protein and fat mass that had been accreted before birth.

Conditions

Very Low Birth Weight Infant

Keywords

intravenous fat emulsions; preterm infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

control group

Begins treatment with 0.5 g/kg per day of 20% Intravenous Lipid Emulsion (IVLE) after birth if the birth weight is less or equal 1000g or 1 g/kg per day if birth weight is more than 1000g. The IVLE dose in this group will be increased by 0.5 g/kg per day daily until reaching 3 g/kg per day.

Group Type: NO_INTERVENTION

No interventions assigned to this group

experimental group

The experimental group will begin treatment with 2 g/kg per day of 20% Intravenous Lipid Emulsion after birth.

The dose of IVLE will be increased directly from 2 to 3 g/kg per day the next day in this group.

Group Type: EXPERIMENTAL

Intravenous lipid emulsion

Intervention Type: OTHER

using higher dose of IV lipids after birth

Interventions

Intravenous lipid emulsion

using higher dose of IV lipids after birth

Intervention Type: OTHER

Other Intervention Names

Intralipid

Eligibility Criteria

Inclusion Criteria

1. Preterm infants born with birth weight < 1500 g

2. Appropriate for gestational age (AGA)

3. Anticipated duration of PN for >7 days

Exclusion Criteria

1. Infants with congenital anomalies

2. Infants with suspected inborn errors of metabolism or family history of inborn error of metabolism

3. Infants with suspected or confirmed biliary atresia

4. Infants born small for gestational age (SGA)

5. Confirmed early sepsis

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belal Alshaikh

OTHER

Sponsor Role: lead

Responsible Party

Belal Alshaikh

Neonatologist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Belal Alshaikh, MD,MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Foothills Medical Centre

Calgary, Alberta, Canada

Countries

Canada

References

Alburaki W, Yusuf K, Dobry J, Sheinfeld R, Alshaikh B. High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial. J Pediatr. 2021 Jan;228:16-23.e1. doi: 10.1016/j.jpeds.2020.08.024. Epub 2020 Aug 13.

Reference Type: DERIVED

PMID: 32798567 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

REB17-2236

Identifier Type: -

Identifier Source: org_study_id