Late Preterm Corticosteroids and Neonatal Hypoglycemia

Timing of Late Preterm Corticosteroid Administration and Neonatal Hypoglycemia

This is a prospective randomized controlled trial investigating the timing of betamethasone administration in late preterm infants in relation to delivery and impact on neonatal hypoglycemia. Previous data has shown that neonatal hypoglycemia is increased in late preterm infants that were exposed to antenatal corticosteroids. The investigators hypothesize that the timing of steroid administration may impact the development of neonatal hypoglycemia.

Study Overview

• Status: Not yet recruiting
• Conditions: Prematurity; Neonatal Hypoglycemia
• Intervention / Treatment: Drug: Betamethasone Sodium Phosphate

Detailed Description

The use of antenatal corticosteroids for women at risk for preterm delivery has become widely adopted as standard of care. The American College of Obstetrics and Gynecologists (ACOG) officially recommends the use of corticosteroids for pregnant women between 24 and 34 weeks of gestation at risk of delivery within 7 days. Since publication of the ALPS trial, the Society of Maternal Fetal Medicine (SMFM) published guidelines supporting the use of late preterm steroids for singleton pregnancies between 34 weeks 0 days and 36 weeks 6 days who are at high risk of preterm birth within 7 days.

A secondary finding of the ALPS trial included the observation that the administration of antenatal betamethasone significantly increased the rate of neonatal hypoglycemia; the authors emphasized that while the long-term risks associated with neonatal hypoglycemia are not fully known, significant hypoglycemia is associated with poor neurodevelopmental outcome.

The optimal interval for administering late preterm steroids before delivery to minimize the risks of hypoglycemia while maximizing the benefits of fetal lung maturity has not been identified. The proposed research study will further investigate this question by randomizing patients to receive late preterm corticosteroids 2 days before delivery versus 7 days before delivery in order to determine if the rates and severity of neonatal hypoglycemia are different.

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elizabeth Sasso; Phone Number: 3234093536; Email: elizabeth.sasso@med.usc.edu
• Study Contact Backup: Name: Genevieve Mazza; Email: genevieve.mazza@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • LAC+USC Medical Center
      • Contact: Genevieve Mazza; Email: genevieve.mazza@med.usc.edu
      • Contact: Elizabeth Sasso; Email: elizabeth.sasso@med.usc.edu
      • Principal Investigator: Elizabeth Sasso, MD
      • Sub-Investigator: Genevieve Mazza, MD
      • Sub-Investigator: Kristen Uquillas, MD
      • Sub-Investigator: Michelle Nguyen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Singleton pregnancy
• Gestational age 34 0/7 weeks to 36 5/7 weeks
• Planned delivery in late preterm period

Exclusion Criteria:

• Prior course of betamethasone during pregnancy
• Twin gestation
• Fetal demise
• Major fetal anomaly
• Maternal contraindication to betamethasone
• Pregestational diabetes
• Expected delivery within 12 hours of randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Late Preterm Steroids 2 Days	Drug: Betamethasone Sodium Phosphate; Betamethasone Sodium Phosphate 12mg IM q24h for 2 doses; Other Names: Celestone
Active Comparator: Late Preterm Steroids 7 Days	Drug: Betamethasone Sodium Phosphate; Betamethasone Sodium Phosphate 12mg IM q24h for 2 doses; Other Names: Celestone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Glucose Concentration	Glucose reported in mg/dL; Hypoglycemia defined as concentration < 40 mg/dL	Delivery to 72 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Days in hospital from date of delivery until date of discharge	Delivery to discharge from hospital
Use of CPAP or High Flow Nasal Cannula	Drop in oxygen saturation requiring use of CPAP or high flow nasal cannula for at least 12 continuous hours	Delivery to 72 hours of life
Need for supplemental oxygen	Drop in oxygen saturation requiring use of supplemental oxygen with a fraction of inspired oxygen (FiO2) of at least 0.30 for at least 24 continuous hours	Delivery to 72 hours of life
Use of ECMO	Drop in oxygen saturation requiring use of ECMO (extracorporeal membrane oxygenation)	Delivery to 72 hours of life
Use of mechanical ventilation	Drop in oxygen saturation and/or inability to maintain an airway requiring use of mechanical ventilation	Delivery to 72 hours of life
Stillbirth	Incidence of intrauterine fetal demise at any point after administration of the intervention (betamethasone) and before delivery	From administration of the intervention (betamethasone) to delivery
Neonatal death	Death of fetus after delivery	Delivery to 30 days of life
Respiratory distress syndrome (RDS)	Defined as the presence of clinical signs of respiratory distress (ie: tachypnea, retractions, flaring, grunting, cyanosis) with a requirement of supplemental oxygen with a fraction of inspired oxygen of more than 0.21 and a chest radiograph showing hypoaeration and reticulogranular infiltrates	Delivery to 72 hours of life
Transient Tachypnea of the Newborn	Defined when tachypnea (Respiratory Rate >60 breaths per minute) occurs in the absence of chest radiography or a radiograph that was normal and resolved within 72 hours	Delivery to 72 hours of life
Need for surfactant administration	Need for administration of exogenous surfactant in the setting of neonatal respiratory distress	Delivery to 72 hours of life
Neonatal pneumonia	Defined when a combination of clinical, microbiologic, and/or radiographic findings suggest primary pulmonary infection as a cause of respiratory distress, fevers, increasing white blood cell count, need for antibiotics, and/or sepsis.	Delivery to 72 hours of life

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for resuscitation at birth	Any intervention in the first 30 minutes, excluding blow-by oxygen	Within 30 minutes of delivery
Neonatal Hypothermia	Defined as rectal temperature below 36 degrees Celsius	Delivery to 72 hours of life
Necrotizing Entercolitis	When systemic, radiographic, and abdominal signs lead to a modified Bell stage 2 or 3	Delivery to 72 hours of life
Intraventricular Hemorrhage Grade 3 or 4 (Severe IVH)	Defined when the extent of brain injury includes a hemorrhage that occupies more than 50% of the lateral ventricle volume	Delivery to 72 hours of life
Feeding Difficulty	inability to take all feeds by mouth, requiring gavage feeds or intravenous supplementation at least once.	Delivery to 72 hours of life

Collaborators and Investigators

• Sponsor: University of Southern California

Publications and helpful links

General Publications

• Practice Bulletin No. 159: Management of Preterm Labor. Obstet Gynecol. 2016 Jan;127(1):e29-e38. doi: 10.1097/AOG.0000000000001265.
• Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972 Oct;50(4):515-25. No abstract available.
• Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, Rouse DJ, McKenna DS, Clark EA, Thorp JM Jr, Chien EK, Peaceman AM, Gibbs RS, Swamy GK, Norton ME, Casey BM, Caritis SN, Tolosa JE, Sorokin Y, VanDorsten JP, Jain L; NICHD Maternal-Fetal Medicine Units Network. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016 Apr 7;374(14):1311-20. doi: 10.1056/NEJMoa1516783. Epub 2016 Feb 4.
• Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016 Aug;215(2):B13-5. doi: 10.1016/j.ajog.2016.03.013. Epub 2016 Mar 15. No abstract available. Erratum In: Am J Obstet Gynecol. 2017 Feb;216(2):180.
• Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: What do we do now? Am J Obstet Gynecol. 2016 Oct;215(4):423-30. doi: 10.1016/j.ajog.2016.06.023. Epub 2016 Jun 21.
• Uquillas KR, Lee RH, Sardesai S, Chen E, Ihenacho U, Cortessis VK, Barton L. Neonatal hypoglycemia after initiation of late preterm antenatal corticosteroids. J Perinatol. 2020 Sep;40(9):1339-1348. doi: 10.1038/s41372-020-0589-1. Epub 2020 Feb 14.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone sodium phosphate
• Other Study ID Numbers: APP-21-01310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No