Clinical trial NCT03076775: Euglycemia After Antenatal Late Preterm Steroids, the E-ALPS Study
Official title: Fetal Metabolic Consequences of Late Preterm Steroid Exposure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy Preterm
Neonatal Hypoglycemia
Hyperglycemia Drug Induced
Keywords: Betamethasone
Late preterm
Steroids
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-03-10
Enrollment: 86
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Annually in the U.S 300,000 neonates are born late preterm, defined as 34 weeks 0 days - 36 weeks 6 days. The Antenatal Late Preterm Steroids (ALPS) Trial demonstrated that maternal treatment with betamethasone in the late preterm period significantly reduces neonatal respiratory complications, but also increases neonatal hypoglycemia, compared to placebo.

This research study will attempt to answer the following primary question: Does a management protocol aimed at maintaining maternal euglycemia after ALPS decrease fetal hyperinsulinemia, compared to usual antepartum care?

Detailed description: Euglycemia after Antenatal Late Preterm Steroids, the E-ALPS Study:

There is a fundamental gap in understanding the adverse metabolic effects of antenatal late preterm steroids (ALPS). In 2016, an important randomized clinical trial of 2827 late preterm pregnancies showed that antenatal betamethasone (BMZ) significantly reduced neonatal respiratory complications compared with placebo. However, those neonates exposed to BMZ were also more likely to have hypoglycemia at birth. This unexpected adverse outcome raised concern among both obstetricians and neonatologists and remains an important knowledge gap to be filled. The rationale for the proposed research is that steroid-induced maternal hyperglycemia leads to transient fetal hyperinsulinemia, which causes hypoglycemia in neonates that are delivered during this time-period. Thus, the fetal metabolic consequences and subsequent neonatal hypoglycemia observed after exposure to BMZ in utero can be prevented by achieving maternal euglycemia prior to delivery.

This protocol describes a randomized clinical trial to evaluate whether screening for and treatment of steroid-induced hyperglycemia in non-diabetic women treated with BMZ in the late preterm period can decrease the rate of fetal hyperinsulinemia, thus reducing neonatal hypoglycemia and improving short-term neonatal outcomes.

This study was formerly approved as Institutional Review Board #16-3200.

Eligibility criteria: Inclusion Criteria:

* Singleton gestation with no known major fetal anomalies
* Gestational age at randomization between 34 weeks 0 days and 36 weeks 5 days
* Receiving antenatal betamethasone due to high probability of delivery in late preterm period

Exclusion Criteria:

* Pre-gestational or gestational diabetes mellitus
* Maternal contraindication to insulin
* Planned outpatient treatment with antenatal betamethasone
* Participation in clinical trial that could affect primary outcome or participation in this trial in a previous pregnancy

Primary outcomes:
measure: Umbilical Cord Blood C-peptide
timeFrame: At delivery
Secondary outcomes:
measure: Umbilical Cord Blood Cortisol
timeFrame: At delivery
measure: Umbilical Insulin-Like Growth Factor 1
timeFrame: At delivery
measure: Umbilical Cord Blood Leptin
timeFrame: At delivery
measure: Neonatal Hypoglycemia
timeFrame: After birth, up to 48 hours of life
measure: Neonatal Hypoglycemia Treatment
timeFrame: After birth, during hospital admission, assessed up to 28 days
measure: Neonatal Glucose Nadir
timeFrame: After birth, during hospital admission, assessed up to 28 days
measure: Timing of Neonatal Blood Glucose Nadir
timeFrame: After birth, during hospital admission, assessed up to 28 days
measure: Neonatal Intensive Care Unit Admission
timeFrame: Date of delivery to date of discharge from hospital, assessed up to 28 days
measure: Neonatal Intensive Care Unit Length of Stay
timeFrame: From neonatal intensive care unit admission to discharge, assessed up to 28 days
measure: Neonatal Seizures
timeFrame: After birth, during hospital admission, assessed up to 28 days
measure: Neonatal Mortality
timeFrame: After birth, during hospital admission, assessed up to 28 days
measure: Maternal Hyperglycemia
timeFrame: For five days after first dose of betamethasone administration
measure: Maternal Insulin Treatment
timeFrame: For five days after first dose of betamethasone administration
measure: Maternal Hypoglycemia
timeFrame: For five days after first dose of betamethasone administration
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: University of Alabama at Birmingham
name: Ashley N Battarbee, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Kim Boggess, MD
role: PRINCIPAL_INVESTIGATOR
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