Am J Perinatol 2023; 40(05): 532-538
DOI: 10.1055/s-0041-1729561
Original Article

Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study

Cynthia Gyamfi-Bannerman
1   Department of Obstetrics and Gynecology, Columbia University, New York City, New York
,
Kathleen A. Jablonski
2   Department of Epidemiology, George Washington University Biostatistics Center, Washington, District of Columbia
,
Sean C. Blackwell
3   Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center, Children's Memorial Hermann Hospital, Houston, Texas
,
Alan T. N. Tita
4   Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
,
Uma M. Reddy
5   Department of Obstetrics, Gynecology, and Reproductive Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
,
Lucky Jain
6   Department of Pediatrics, Emory University, Atlanta, Georgia
,
George R. Saade
7   Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
,
Dwight J. Rouse
8   Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island
,
Erin A. S. Clark
9   Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah
,
John M. Thorp Jr.
10   Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
,
Edward K. Chien
11   Department of Obstetrics and Gynecology Specialists, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
,
Alan M. Peaceman
12   Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois
,
13   Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado
,
Geeta K. Swamy
14   Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina
,
Mary E. Norton
15   Department of Obstetrics, Gynecology, and Reproductive Sciences, Stanford University, Stanford, California
,
Brian M. Casey
16   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Steve N. Caritis
17   Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Jorge E. Tolosa
18   Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon
,
Yoram Sorokin
19   Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
,
J. Peter VanDorsten
20   Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina
,
for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network › Author Affiliations
Funding This study received support by grants (HL098554 and HL098354) from the NHLBI, by grants (HD21410, HD27915, HD27917, HD27869, HD34116, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, HD53097, HD53118, HD68268, HD68258, HD68282, and HD36801) from the NICHD, and by a grant (UL1 TR000040) from the National Center for Advancing Translational Sciences, National Institutes of Health. The comments and views expressed in this article are those of the authors and do not necessarily represent the views of the National Institutes of Health. C.G.B. reports grants from NICHD, grants from NHLBI, during the conduct of the study; grants from SMFM/AMAG, personal fees from Sera Prognostics, outside the submitted work.

Abstract

Objective In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia.

Study Design Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate.

Results Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46–1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03–7.03) vs. 3.74 (interquartile range: 2.15–15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18).

Conclusion In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure.

Key Points

  • Hypoglycemia was transient and approximately two-thirds received no treatment.

  • Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.

  • Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure.

* Additional members of this network are listed in [ Supplementary Material ] (available in the online version).


Supplementary Material



Publication History

Received: 08 October 2020

Accepted: 16 March 2021

Article published online:
27 May 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics 2004; 114 (02) 372-376
  • 2 Escobar GJ, Clark RH, Greene JD. Short-term outcomes of infants born at 35 and 36 weeks gestation: we need to ask more questions. Semin Perinatol 2006; 30 (01) 28-33
  • 3 Adamkin DH. Committee on Fetus and Newborn. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127 (03) 575-579
  • 4 Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161 (05) 787-791
  • 5 Cornblath M, Hawdon JM, Williams AF. et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000; 105 (05) 1141-1145
  • 6 Rozance PJ, Hay WW. Hypoglycemia in newborn infants: features associated with adverse outcomes. Biol Neonate 2006; 90 (02) 74-86
  • 7 Kalhan S, Parimi P. Gluconeogenesis in the fetus and neonate. Semin Perinatol 2000; 24 (02) 94-106
  • 8 Hawdon JM, Ward Platt MP, Aynsley-Green A. Patterns of metabolic adaptation for preterm and term infants in the first neonatal week. Arch Dis Child 1992; 67 (4 Spec No): 357-365
  • 9 Gyamfi-Bannerman C, Thom EA, Blackwell SC. et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med 2016; 374 (14) 1311-1320
  • 10 Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972; 50 (04) 515-525
  • 11 Thompson-Branch A, Havranek T. Neonatal hypoglycemia. Pediatr Rev 2017; 38 (04) 147-157
  • 12 Sterne JA, White IR, Carlin JB. et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ 2009; 338: b2393
  • 13 Gardiner RM. The effects of hypoglycaemia on cerebral blood flow and metabolism in the new-born calf. J Physiol 1980; 298: 37-51
  • 14 Heck LJ, Erenberg A. Serum glucose levels in term neonates during the first 48 hours of life. J Pediatr 1987; 110 (01) 119-122
  • 15 Sinclair JC. Approaches to the definition of neonatal hypoglycemia. Acta Paediatr Jpn 1997; 39 (suppl 1): S17-S20
  • 16 Morales WJ, Diebel ND, Lazar AJ, Zadrozny D. Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol 1981; 141 (03) 276-287
  • 17 Balci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest 2010; 70 (02) 95-99
  • 18 Garite TJ, Rumney PJ, Briggs GG. et al. A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24 to 28 weeks' gestation. Am J Obstet Gynecol 1992; 166 (02) 646-651
  • 19 Gamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. Br J Obstet Gynaecol 1989; 96 (04) 401-410