Outcome of Very Preterm Infants With Glucose Level Disturbances

NCT ID: NCT03530189

Last Updated: 2023-08-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2022-12-31

Brief Summary

The hypothesis of this prospective, cohort study is that hyperglycemia, hypoglycemia and unstable glucose levels in the first seven days of life in infants born very preterm and at very low birth weights can harm long-term neurodevelopment. The objective of the study is to investigate the relationship between early neonatal glycemia, neonatal characteristics, and developmental outcomes in preterm infants. All infants born before 32. gestational week or below 1500 g admitted to the neonatal intensive care unit will be included in the study. According to the glucose values, the infants will be divided into the normoglycemic group and the group with disturbed glucose concentration. In the corrected age of two neurodevelopmental outcome will be assessed and categorized as normal, mild, moderate or severe impairment. Since the results of published studies about the effects of asymptomatic neonatal hypoglycemia and hyperglycemia on neurodevelopment are inconsistent, the correlation between early disturbances in glucose levels and neurodevelopmental outcome will be assessed.

Detailed Description

All infants born before 32 weeks of gestation or weighing <1500 g and admitted to the Neonatal intensive care unit of the University Hospital Center Rijeka will be included into the study. The investigators will collect data from the neonatal period, including: gestational age, sex, birth weight, Apgar score at 1 and 5 minutes, socioeconomic status and Clinical Risk Index for Babies scoring system (CRIB II). Blood glucose levels will be measured at 3rd, 12th, and 18th hour after birth on the first day of life, and from the 2nd to the 7th day of life blood glucose levels will be measured once a day. According to the blood glucose concentrations infants will be divided into normoglycemic group and group with disturbed glucose concentration. The relationship between glycemia category and 2-year outcomes will be investigated. In the corrected age of two years neurodevelopmental outcome will be assessed. Certified psychologists will assess cognitive, motor and language development with the Bayley Scales of Infant and Toddler Development (Bayley III). Bayley III scales are standardized to a mean (SD) score of 100. Pediatric neurologists or pediatrics will examine the children and will estimate the neuromotor function. Cognitive, motor and language development were considered normal if the composite score on the respective Bayley-III score was ≥mean -1SD; mildly impaired if the score was < -1 SD and ≥ -2 SD; moderately impaired if the score was <-2 SD and ≥3 SD; and severely impaired if the score was < mean -3SD.

Cerebral palsy (CP) was evaluated according to the European Cerebral Palsy Network definition. The severity of CP was classified as mild in children who were able to walk without an aid, moderate in children able to walk with an aid, and severe in children who were unable to walk even with an aid.

Children unable to fixate and follow a light with either eye were considered bilaterally blind. Children registered at low-vision centers without blindness were recorded as having moderate visual impairment. Severe auditory impairment was defined as hearing loss that could not be corrected with a hearing aid and moderate auditory impairment was defined as hearing loss corrected with a hearing aid.

The overall outcome was categorized as normal, mild, moderate or severe impairment. Mild impairment was defined as scores between -1and -2 standard deviations from the mean of any of the Bayley-III scales or mild CP. Moderate impairment was defined as scores between -2and -3 standard deviations from the mean of any of the Bayley-III scales, moderate CP, or moderate visual or hearing impairment. Severe impairment was defined as scores between < mean -3 standard deviations of any of the Bayley-III scales, severe CP, or bilateral blindness or deafness.

Conditions

Cerebral Palsy Infantile

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Normoglycemic group

The infant will enter this group if a single blood glucose concentration is between 2.1 and 2.5 mmol/l (38-45 mg/dL), or a single blood glucose concentration is between 8.6 - 10 mmol/l (155-180 mg/dL) with all other measures between 2.6 and 8.5 mmol/l (47-153 mg/dL).

To all premature infants intravenous 10% dextrose at 60-90 mL/kg/day will be started as soon as possible after birth.

10% dextrose

Intervention Type: DRUG

After birth the intravenous 10% dextrose at 60-90 ml/kg/day will be started as soon as possible

Group with impaired glucose

The infant can be hypoglycemic, hyperglycemic or unstable. The infant will be hypoglycemic if blood glucose concentration is ≤2,5 mmol/l (45 mg/dL) on ≥2 measures >1 hour apart, or any blood glucose concentration is≤2,0 mmol/l (36 mg/dL). Hypoglycemia will be treated with intravenous bolus of 10% dextrose.

The infant will be hyperglycemic if blood glucose concentration is ≥8,6 mmol/l (155 mg/dL) on ≥2 measures >1 hour apart, or any blood glucose concentration ≥10,1 mmol/l (182 mg/dL). Hyperglycemia will be managed by reducing the glucose infusion rate or initiation of an insulin infusion.

The infant will be unstable if at least 1 blood glucose concentration is ≤2,5 mmol/l (45 mg/dL) and ≥1 blood glucose concentration is ≥8,6 mmol/l (155 mg/dL).

bolus of dextrose, reducing the glucose infusion, insulin

Intervention Type: DRUG

Hypoglycemia will be treated with 2 mL/kg to 3 mL/kg (200-300 mg/kg) intravenous bolus of 10% dextrose.

Hyperglycemia will be managed by reducing the glucose infusion rate or initiation of an insulin infusion.

Interventions

10% dextrose

After birth the intravenous 10% dextrose at 60-90 ml/kg/day will be started as soon as possible

Intervention Type: DRUG

bolus of dextrose, reducing the glucose infusion, insulin

Hypoglycemia will be treated with 2 mL/kg to 3 mL/kg (200-300 mg/kg) intravenous bolus of 10% dextrose.

Hyperglycemia will be managed by reducing the glucose infusion rate or initiation of an insulin infusion.

Intervention Type: DRUG

Other Intervention Names

There is no other intervention names; There is no other intervention names

Eligibility Criteria

Inclusion Criteria

• infants born weighing <1500 g or at <32 weeks of gestation

Exclusion Criteria

• infants with significant congenital abnormalities
• infants died before day 7
• infants whose mothers suffer from type 1, type 2 diabetes mellitus or gestational diabetes

• Minimum Eligible Age: 24 Weeks
• Maximum Eligible Age: 27 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Rijeka

OTHER

Sponsor Role: lead

Responsible Party

Ivona Butorac Ahel

Ivona Butorac Ahel, MD, MS, principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ivona Butorac Ahel, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University Hospital Center Rijeka, 51 000 Rijeka, Croatia

Locations

University Hospital Center Rijeka

Rijeka, , Croatia

Countries

Croatia

References

Tottman AC, Alsweiler JM, Bloomfield FH, Gamble G, Jiang Y, Leung M, Poppe T, Thompson B, Wouldes TA, Harding JE; PIANO Study Group. Long-Term Outcomes of Hyperglycemic Preterm Infants Randomized to Tight Glycemic Control. J Pediatr. 2018 Feb;193:68-75.e1. doi: 10.1016/j.jpeds.2017.09.081. Epub 2017 Dec 1.

Reference Type: BACKGROUND

PMID: 29198539 (View on PubMed)

Sinclair JC, Bottino M, Cowett RM. Interventions for prevention of neonatal hyperglycemia in very low birth weight infants. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD007615. doi: 10.1002/14651858.CD007615.pub3.

Reference Type: BACKGROUND

PMID: 21975772 (View on PubMed)

Mitanchez D. Glucose regulation in preterm newborn infants. Horm Res. 2007;68(6):265-71. doi: 10.1159/000104174. Epub 2007 Jun 20.

Reference Type: BACKGROUND

PMID: 17587854 (View on PubMed)

Goode RH, Rettiganti M, Li J, Lyle RE, Whiteside-Mansell L, Barrett KW, Casey PH. Developmental Outcomes of Preterm Infants With Neonatal Hypoglycemia. Pediatrics. 2016 Dec;138(6):e20161424. doi: 10.1542/peds.2016-1424. Epub 2016 Nov 4.

Reference Type: BACKGROUND

PMID: 27940690 (View on PubMed)

Tin W, Brunskill G, Kelly T, Fritz S. 15-year follow-up of recurrent "hypoglycemia" in preterm infants. Pediatrics. 2012 Dec;130(6):e1497-503. doi: 10.1542/peds.2012-0776. Epub 2012 Nov 5.

Reference Type: BACKGROUND

PMID: 23129080 (View on PubMed)

Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988 Nov 19;297(6659):1304-8. doi: 10.1136/bmj.297.6659.1304.

Reference Type: BACKGROUND

PMID: 2462455 (View on PubMed)

Hey E. Hyperglycaemia and the very preterm baby. Semin Fetal Neonatal Med. 2005 Aug;10(4):377-87. doi: 10.1016/j.siny.2005.04.008.

Reference Type: BACKGROUND

PMID: 15927546 (View on PubMed)

Decaro MH, Vain NE. Hyperglycaemia in preterm neonates: what to know, what to do. Early Hum Dev. 2011 Mar;87 Suppl 1:S19-22. doi: 10.1016/j.earlhumdev.2011.01.005. Epub 2011 Jan 26.

Reference Type: BACKGROUND

PMID: 21276670 (View on PubMed)

Surveillance of Cerebral Palsy in Europe. Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers. Surveillance of Cerebral Palsy in Europe (SCPE). Dev Med Child Neurol. 2000 Dec;42(12):816-24. doi: 10.1017/s0012162200001511.

Reference Type: BACKGROUND

PMID: 11132255 (View on PubMed)

Other Identifiers

istrazivanje01

Identifier Type: -

Identifier Source: org_study_id