Early hypoglycemia is not an independent risk factor for 2-year cognitive impairment in small for gestational age preterm infants of less than 32 weeks

The objective of this study is to evaluate whether early hypoglycemia is an independent risk factor for 2-year cognitive (COG) impairment in small for gestational age (SGA) preterm infants with gestational age (GA) < 32 weeks. We retrospectively reviewed data of 1364 preterm infants with a GA 24^+0/7-31^+6/7 weeks. Infants were classified based on blood glucose concentrations within the first 6 h of life (HOL) as < or ≥ 40 mg/dL (Glyc < 40^[Birth-6HOL] and Glyc ≥ 40^[Birth-6HOL], respectively) and subsequently by birth weight z-score as SGA or appropriate for gestational age (AGA). Propensity score matching analyses were conducted for each comparison. Multiple logistic regression was used to evaluate the association of Glyc < 40^[Birth-6HOL] with 2-year COG impairment, defined as a Bayley-III score < 85, in SGA infants. Out of the 747 preterm infants who met the inclusion criteria, 173 (23.2%) were classified as Glyc < 40^[Birth-6HOL], and 574 (76.8%) as Glyc ≥ 40^[Birth-6HOL]. The proportion of SGA infants was significantly higher in Glyc < 40^[Birth-6HOL] than in Glyc ≥ 40^[Birth-6HOL] (25.4 vs 18.3%, p = 0.039). The incidence of 2-year COG impairment was significantly higher in SGA infants compared to matched AGA counterparts both in Glyc < 40^[Birth-6HOL] (+ 20%, p = 0.040) and Glyc ≥ 40^[Birth-6HOL] (+ 17%, p = 0.029). Neither in the entire cohort nor in the SGA infants, Glyc < 40^[Birth-6HOL] was significantly associated with 2-year COG impairment (aOR: 1.077, p = 0.768; 0.993, p = 0.935; respectively) after the adjustment for GA, sex, Apgar score at 5 min < 7, SGA status, complications of prematurity, duration of mechanical ventilator support > 7 days, cumulative energy intakes from birth to 36 weeks, and maternal university level.

Conclusion: Among SGA preterm infants with GA between 24^+0/7 and 31^+6/7 weeks/days, hypoglycemia within the first 6 HOL was not an independent risk factor for 2-year COG impairment.

What is known: • Hypoglycemia is associated with poor neurodevelopmental outcomes in preterm infants. • Small for gestational age (SGA) preterm infants are more prone to cognitive (COG) impairment compared to AGA counterparts.

What is new: • In a large cohort of preterm infants < 32 weeks, the incidence of hypoglycemia within the first 6 hours of life (HOL) was higher in SGA compared to AGA. • Hypoglycemia within the first 6 HOL was not an independent risk factor for 2-year COG impairment in SGA preterm infants.