Euglycemia After Antenatal Late Preterm Steroids, the E-ALPS Study

Not Applicable

Completed

Conditions: Neonatal Hypoglycemia
Hyperglycemia Drug Induced
Pregnancy Preterm

Interventions: Other: Maternal glycemic control

Registration Number: NCT03076775

Lead Sponsor: University of North Carolina, Chapel Hill

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 86

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Maternal glycemic control	Women will undergo regular maternal blood glucose screening and treatment of hyperglycemia following BMZ administration to achieve maternal glycemic control until delivery or hospital discharge, for a maximum of 5 days.

Primary Outcome Measures

Name	Time	Method
Umbilical Cord Blood C-peptide	At delivery	C-peptide level (ng/mL) as measure of fetal hyperinsulinemia

Secondary Outcome Measures

Name	Time	Method
Umbilical Insulin-Like Growth Factor 1	At delivery	Insulin-like growth factor 1 level (ng/mL) as a measure of in utero metabolic status
Neonatal Hypoglycemia	After birth, up to 48 hours of life	Number of neonates with capillary blood glucose \< 40 mg/dL
Maternal Hyperglycemia	For five days after first dose of betamethasone administration	Number of mothers with intrapartum capillary blood glucose \>110 mg/dL, fasting capillary blood glucose \>95 mg/dL, or 1-hour postprandial capillary blood glucose \>140 mg/dL
Maternal Insulin Treatment	For five days after first dose of betamethasone administration	Number of mothers who received insulin for treatment of hyperglycemia
Umbilical Cord Blood Cortisol	At delivery	Cortisol level (ug/mL) as measure of fetal immune suppression
Neonatal Intensive Care Unit Admission	Date of delivery to date of discharge from hospital, assessed up to 28 days	Number of neonates admitted to the neonatal intensive care unit for \> 24 hours
Timing of Neonatal Blood Glucose Nadir	After birth, during hospital admission, assessed up to 28 days	Number of hours after birth when lowest neonatal capillary blood glucose was measured
Neonatal Seizures	After birth, during hospital admission, assessed up to 28 days	Number of neonates who had seizures
Maternal Hypoglycemia	For five days after first dose of betamethasone administration	Number of mothers with capillary blood glucose \<60 mg/dL
Umbilical Cord Blood Leptin	At delivery	Leptin level (ng/mL) as measure of fetal adiposity
Neonatal Intensive Care Unit Length of Stay	From neonatal intensive care unit admission to discharge, assessed up to 28 days	Number of days of neonatal intensive care unit stay
Neonatal Hypoglycemia Treatment	After birth, during hospital admission, assessed up to 28 days	Number of neonates with hypoglycemia requiring treatment with dextrose gel or dextrose intravenous fluids
Neonatal Glucose Nadir	After birth, during hospital admission, assessed up to 28 days	Lowest neonatal capillary blood glucose (mg/dL)
Neonatal Mortality	After birth, during hospital admission, assessed up to 28 days	Number of neonates who died

Trial Locations

Locations (2): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of North Carolina - Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States