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Am J Perinatol 2023; 40(10): 1096-1105
DOI: 10.1055/s-0041-1732380
Original Article

Early Transient Hypoglycemia and Test Performance in At-Risk Newborns

Nahed O. ElHassan 
1   Department of Pediatrics (Neonatal-Perinatal Medicine), University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas
,
Eric W. Schaefer
2   Division of Biostatistics, Penn State College of Medicine, Hershey, Pennsylvania
,
Basilia Gonzalez
3   Department of Family Medicine, Lifelong Medicare Care, Richmond, California
,
Thomas Nienaber 
1   Department of Pediatrics (Neonatal-Perinatal Medicine), University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas
,
Luc P. Brion 
4   Department of Pediatrics (Neonatal-Perinatal Medicine), University of Texas Southwestern Medical Center, Dallas, Texas
,
Jeffrey R. Kaiser
5   Departments of Pediatrics (Neonatal-Perinatal Medicine) and Obstetrics and Gynecology, Penn State Health Children's Hospital, Hershey, Pennsylvania
› Author Affiliations Funding None.
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Abstract

Objective This study aimed to evaluate if early (within the first 3 hours after birth) transient neonatal hypoglycemia (TNH) is associated with poor academic performance in infants at-risk for hypoglycemia.

Study Design This was a retrospective cohort study of at risk-infants (late preterm infants, small and large for gestational age infants, and infants of diabetic mothers [IDMs]) who were born in 1998 and 1999 at the University of Arkansas for Medical Sciences and had ≥1 recorded glucose concentration. The outcome measure was proficiency on 4th grade literacy and mathematics achievement tests. Three glucose concentration cutoffs for defining hypoglycemia (<35, <40, and <45 mg/dL) were investigated. Logistic regression models were developed to examine the association between early TNH and achievement test proficiency based on perinatal factors.

Results Among 726 infants, 472 had one, 233 had two, and 21 had three risk factor(s). Early TNH (glucose concentration <35, <40, and <45 mg/dL) was observed in 6.3, 11.6, and 20.5% of the study cohort, respectively. Irrespective of the cutoff used, the frequency of early TNH (number of patients with early TNH in a risk category divided by the total number of patients in that category) was significantly greater among infants with multiple risk factors. After controlling for perinatal factors, early TNH (cutoffs <35 and <40 mg/dL) was significantly associated with decreased probability of proficiency in literacy but not mathematics. Despite that early TNH was more common in IDMs and infants with three risk factors, the category or number of risk factors did not impact academic proficiency.

Conclusion Early TNH (<35 and <40 mg/dL) was associated with lower adjusted probability of proficiency on 4th grade literacy achievement tests in at-risk infants. The impact of early TNH on academic performance was similar irrespective of category or number of risk factors.

Key Points

  • Transient hypoglycemia was associated with lower proficiency on 4th grade tests in at-risk infants.

  • The category of risk factors among at-risk infants did not impact 4th grade academic proficiency.

  • The number of risk factors among at-risk infants did not impact 4th grade academic proficiency.

Keywords

hypoglycemia - infant of diabetic mothers - large for gestational age - small for gestational age - late preterm

Note

The abstract and the preliminary findings of this article were presented (poster) at the Society for Pediatric Research, Baltimore, MD.




Publication History

Received: 20 February 2021

Accepted: 15 June 2021

Article published online:
30 July 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Hay Jr WW, Raju TN, Higgins RD, Kalhan SC, Devaskar SU. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr 2009; 155 (05) 612-617
    CrossrefPubMedGoogle Scholar
  • 2 Cornblath M, Hawdon JM, Williams AF. et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000; 105 (05) 1141-1145
    CrossrefPubMedGoogle Scholar
  • 3 Cornblath M, Ichord R. Hypoglycemia in the neonate. Semin Perinatol 2000; 24 (02) 136-149
    CrossrefPubMedGoogle Scholar
  • 4 Adamkin DH. Committee on Fetus and Newborn. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127 (03) 575-579
    CrossrefPubMedGoogle Scholar
  • 5 Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161 (05) 787-791
    CrossrefPubMedGoogle Scholar
  • 6 Shah R, Harding J, Brown J, McKinlay C. Neonatal glycaemia and neurodevelopmental outcomes: a systematic review and meta-analysis. Neonatology 2019; 115 (02) 116-126
    CrossrefPubMedGoogle Scholar
  • 7 Kaiser JR, Bai S, Gibson N. et al. Association between transient newborn hypoglycemia and fourth-grade achievement test proficiency: a population based study. JAMA Pediatr 2015; 169 (10) 913-921
    CrossrefPubMedGoogle Scholar
  • 8 McKinlay CJD, Alsweiler JM, Anstice NS. et al; Children With Hypoglycemia and Their Later Development (CHYLD) Study Team. Association of neonatal glycemia with neurodevelopmental outcomes at 4.5 years. JAMA Pediatr 2017; 171 (10) 972-983
    CrossrefPubMedGoogle Scholar
  • 9 Thornton PS, Stanley CA, De Leon DD. et al; Pediatric Endocrine Society. Recommendations from the Pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 2015; 167 (02) 238-245
    CrossrefPubMedGoogle Scholar
  • 10 Adamkin DH, Polin RA. Imperfect advice: neonatal hypoglycemia. J Pediatr 2016; 176: 195-196
    CrossrefPubMedGoogle Scholar
  • 11 Rozance RJ, Hay WH. Neonatal hyperglycemia. Neoreviews 2010; 11 (11) e632-e681
    CrossrefPubMedGoogle Scholar
  • 12 Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics 2006; 118 (03) 1207-1214
    CrossrefPubMedGoogle Scholar
  • 13 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87 (02) 163-168
    CrossrefPubMedGoogle Scholar
  • 14 Beard A, Cornblath M, Gentz J. et al. Neonatal hypoglycemia: a discussion. J Pediatr 1971; 79 (02) 314-324
    CrossrefPubMedGoogle Scholar
  • 15 ElHassan NO, Bai S, Gibson N, Holland G, Robbins JM, Kaiser JR. The impact of prematurity and maternal socioeconomic status and education level on achievement-test scores up to 8th grade. PLoS One 2018; 13 (05) e0198083
    CrossrefPubMedGoogle Scholar
  • 16 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (02) 377-381
    Google Scholar
  • 17 Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med 2006; 25 (01) 127-141
    CrossrefPubMedGoogle Scholar
  • 18 Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med 1989; 8 (05) 551-561
    CrossrefPubMedGoogle Scholar
  • 19 Lubchenco LO, Bard H. Incidence of hypoglycemia in newborn infants classified by birth weight and gestational age. Pediatrics 1971; 47 (05) 831-838
    CrossrefPubMedGoogle Scholar
  • 20 Sexson WR. Incidence of neonatal hypoglycemia: a matter of definition. J Pediatr 1984; 105 (01) 149-150
    CrossrefPubMedGoogle Scholar
  • 21 Maayan-Metzger A, Lubin D, Kuint J. Hypoglycemia rates in the first days of life among term infants born to diabetic mothers. Neonatology 2009; 96 (02) 80-85
    CrossrefPubMedGoogle Scholar
  • 22 Agrawal RK, Lui K, Gupta JM. Neonatal hypoglycaemia in infants of diabetic mothers. J Paediatr Child Health 2000; 36 (04) 354-356
    CrossrefPubMedGoogle Scholar
  • 23 Holtrop PC. The frequency of hypoglycemia in full-term large and small for gestational age newborns. Am J Perinatol 1993; 10 (02) 150-154
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 McKinlay CJ, Alsweiler JM, Ansell JM. et al; CHYLD Study Group. Neonatal glycemia and neurodevelopmental outcomes at 2 years. N Engl J Med 2015; 373 (16) 1507-1518
    CrossrefPubMedGoogle Scholar
  • 25 Boluyt N, van kempen A, Offringa M. Neurodevelopment after neonatal hypoglycemia. Pediatrics 2006; 117 (06) 2231-2243
    CrossrefPubMedGoogle Scholar
  • 26 van Kempen AAMW, Eskes PF, Nuytemans DHGM. et al; HypoEXIT Study Group. HypoEXIT Study Group. Lower versus traditional treatment threshold for neonatal hypoglycemia. N Engl J Med 2020; 382 (06) 534-544
    CrossrefPubMedGoogle Scholar
  • 27 Sharp M, DeMauro SB. Counterbalanced comparison of the BSID-II and Bayley-III at eighteen to twenty-two months corrected age. J Dev Behav Pediatr 2017; 38 (05) 322-329
    CrossrefPubMedGoogle Scholar
  • 28 Finn AS, Kraft MA, West MR. et al. Cognitive skills, student achievement tests, and schools. Psychol Sci 2014; 25 (03) 736-744
    CrossrefPubMedGoogle Scholar
  • 29 Grotheer M, Zhen Z, Lerma-Usabiaga G, Grill-Spector K. Separate lanes for adding and reading in the white matter highways of the human brain. Nat Commun 2019; 10 (01) 3675
    CrossrefPubMedGoogle Scholar
  • 30 Ashkenazi S, Black JM, Abrams DA, Hoeft F, Menon V. Neurobiological underpinnings of math and reading learning disabilities. J Learn Disabil 2013; 46 (06) 549-569
    CrossrefPubMedGoogle Scholar
  • 31 Voyer D, Voyer SD. Gender differences in scholastic achievement: a meta-analysis. Psychol Bull 2014; 140 (04) 1174-1204
    CrossrefPubMedGoogle Scholar
  • 32 Lawrence E, Mollborn S. Racial/ethnic patterns of kindergarten school enrollment in the United States. Sociol Forum (Randolph N J) 2017; 32 (03) 635-658
    CrossrefPubMedGoogle Scholar
  • 33 Tin W, Brunskill G, Kelly T, Fritz S. 15-year follow-up of recurrent “hypoglycemia” in preterm infants. Pediatrics 2012; 130 (06) e1497-e1503
    CrossrefPubMedGoogle Scholar