Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Abstract

Importance:

Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear.

Objective:

To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia.

Design, Setting, and Participants:

Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021.

Interventions:

Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth.

Main Outcomes and Measures:

The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance).

Results:

Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes.

Conclusions and Relevance:

Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required.

Trial Registration:

anzctr.org.au Identifier: ACTRN12614001263684.

• Authors: Taygen Edwards, Jane M Alsweiler, Caroline A Crowther, Richard Edlin, Greg D Gamble, Joanne E Hegarty, Luling Lin, Christopher J D McKinlay, Jenny A Rogers, Benjamin Thompson, Trecia A Wouldes, Jane E Harding
• Journal: JAMA (JAMA) Vol. 327 Issue 12 Pg. 1149-1157 (03 22 2022) ISSN: 1538-3598 [Electronic] United States
• PMID: 35315885 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Gels
• Glucose

Topics

• Administration, Oral
• Chemoprevention
• Child, Preschool
• Double-Blind Method
• Female
• Follow-Up Studies
• Gels
• Glucose (administration & dosage, adverse effects)
• Humans
• Hypoglycemia (prevention & control)
• Infant, Newborn
• Male
• Prospective Studies
• Sensation Disorders (chemically induced)
• Time Factors