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

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT03076775
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 86
• Locations: 2
• Arms: 2
• Actual Duration (Months): 53.4
• Patients Per Site: 43
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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?

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Preterm; Neonatal Hypoglycemia; Hyperglycemia Drug Induced	Other: Maternal glycemic control	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Fetal Metabolic Consequences of Late Preterm Steroid Exposure
• Actual Study Start Date: Jun 8, 2017
• Actual Primary Completion Date: Feb 18, 2021
• Actual Study Completion Date: Nov 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention 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.	Other: Maternal glycemic control; Maternal capillary blood glucose testing will be performed according to oral intake status: every 2 hours if not eating (NPO) or fasting and 1-hour postprandial if eating regular meals. Hyperglycemia, defined based on the American Diabetes Association and the American College of Obstetricians and Gynecologists recommendations as well as current practice at study sites, will be treated according to study guidelines based on oral intake status: insulin infusion if NPO and subcutaneous insulin if eating regular meals.
No Intervention: Usual Care Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.

Outcome Measures

Primary Outcome Measures

1. Umbilical Cord Blood C-peptide [At delivery]

   C-peptide level (ng/mL) as measure of fetal hyperinsulinemia

Secondary Outcome Measures

1. Umbilical Cord Blood Cortisol [At delivery]

   Cortisol level (ug/mL) as measure of fetal immune suppression

2. Umbilical Insulin-Like Growth Factor 1 [At delivery]

   Insulin-like growth factor 1 level (ng/mL) as a measure of in utero metabolic status

3. Umbilical Cord Blood Leptin [At delivery]

   Leptin level (ng/mL) as measure of fetal adiposity

4. Neonatal Hypoglycemia [After birth, up to 48 hours of life]

   Number of neonates with capillary blood glucose < 40 mg/dL

5. 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

6. Neonatal Glucose Nadir [After birth, during hospital admission, assessed up to 28 days]

   Lowest neonatal capillary blood glucose (mg/dL)

7. 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

8. 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

9. 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

10. Neonatal Seizures [After birth, during hospital admission, assessed up to 28 days]

    Number of neonates who had seizures

11. Neonatal Mortality [After birth, during hospital admission, assessed up to 28 days]

    Number of neonates who died

12. 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

13. Maternal Insulin Treatment [For five days after first dose of betamethasone administration]

    Number of mothers who received insulin for treatment of hyperglycemia

14. Maternal Hypoglycemia [For five days after first dose of betamethasone administration]

    Number of mothers with capillary blood glucose <60 mg/dL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Ashley N Battarbee, MD, MSCR, University of Alabama at Birmingham
• Principal Investigator: Kim Boggess, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 9, 2018

More Information

Publications

• ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol. 2005 Mar;105(3):675-85.
• American College of Obstetricians and Gynecologists' Committee on Obstetric Practice; Society for Maternal- Fetal Medicine. Committee Opinion No.677: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol. 2016 Oct;128(4):e187-94. doi: 10.1097/AOG.0000000000001715.
• American Diabetes Association. Erratum. Classification and diagnosis of diabetes. Sec. 2. In Standards of Medical Care in Diabetes-2016. Diabetes Care 2016;39(Suppl. 1):S13-S22. Diabetes Care. 2016 Sep;39(9):1653. doi: 10.2337/dc16-er09.
• Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, Gregory K, Haberman S, Hoffman M, Kominiarek MA, Reddy U, Bailit J, Branch DW, Burkman R, Gonzalez Quintero VH, Hatjis CG, Landy H, Ramirez M, VanVeldhuisen P, Troendle J, Zhang J. Respiratory morbidity in late preterm births. JAMA. 2010 Jul 28;304(4):419-25. doi: 10.1001/jama.2010.1015.
• Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol. 2003 Sep;102(3):488-92.
• 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.
• Jolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. Diabetes Res Clin Pract. 2016 Aug;118:98-104. doi: 10.1016/j.diabres.2016.06.005. Epub 2016 Jun 17.
• Kühl C, Andersen GE, Hertel J, Mølsted-Pedersen L. Metabolic events in infants of diabetic mothers during first 24 hours after birth. I. Changes in plasma glucose, insulin and glucagon. Acta Paediatr Scand. 1982 Jan;71(1):19-25.
• Langen ES, Kuperstock JL, Sung JF, Taslimi M, Byrne J, El-Sayed YY. Maternal glucose response to betamethasone administration. Am J Perinatol. 2015 Feb;30(2):143-8. doi: 10.1055/s-0034-1376387. Epub 2014 Jun 10.
• Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: Final Data for 2015. Natl Vital Stat Rep. 2017 Jan;66(1):1.
• McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008 Jan;111(1):35-41. doi: 10.1097/01.AOG.0000297311.33046.73.
• Obenshain SS, Adam PA, King KC, Teramo K, Raivio KO, Räihä N, Schwartz R. Human fetal insulin response to sustained maternal hyperglycemia. N Engl J Med. 1970 Sep 10;283(11):566-70.
• Refuerzo JS, Garg A, Rech B, Ramin SM, Vidaeff A, Blackwell SC. Continuous glucose monitoring in diabetic women following antenatal corticosteroid therapy: a pilot study. Am J Perinatol. 2012 May;29(5):335-8. doi: 10.1055/s-0031-1295642. Epub 2011 Nov 17.
• Shelton SD, Boggess KA, Smith T, Herbert WN. Effect of betamethasone on maternal glucose. J Matern Fetal Neonatal Med. 2002 Sep;12(3):191-5.
• Sifianou P, Thanou V, Karga H. Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation. J Pediatr Pharmacol Ther. 2015 Mar-Apr;20(2):138-43. doi: 10.5863/1551-6776-20.2.138.
• 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. Review. Erratum in: Am J Obstet Gynecol. 2017 Feb;216(2):180.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT03076775
• Other Study ID Numbers: 18-1970; 1R03HD096188-01
• First Posted: Mar 10, 2017
• Last Update Posted: Jan 26, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of North Carolina, Chapel Hill: Betamethasone; Late preterm; Steroids
• Additional relevant MeSH terms: Premature Birth; Hypoglycemia; Hyperglycemia

Study Results

Participant Flow

Arm/Group Title	Intervention	Usual Care
Arm/Group Description	Women will undergo regular maternal blood glucose screening and treatment of hyperglycemia following Betamethasone (BMZ) administration to achieve maternal glycemic control until delivery or hospital discharge, for a maximum of 5 days. Maternal glycemic control: Maternal capillary blood glucose testing will be performed according to oral intake status: every 2 hours if not eating (NPO) or fasting and 1-hour postprandial if eating regular meals. Hyperglycemia, defined based on the American Diabetes Association and the American College of Obstetricians and Gynecologists recommendations as well as current practice at study sites, will be treated according to study guidelines based on oral intake status: insulin infusion if NPO and subcutaneous insulin if eating regular meals.	Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.
Period Title: Overall Study
STARTED	44	42
Neonates Born During Study	43	42
Umbilical Cord Blood Collected	33	38
COMPLETED	43	42
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Intervention	Usual Care	Total
Arm/Group Description	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.	Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.	Total of all reporting groups
Overall Participants	43	42	85
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	27	28	28
Sex: Female, Male (Count of Participants)
Female	43 100%	42 100%	85 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic Black	17 39.5%	16 38.1%	33 38.8%
Non-Hispanic White	17 39.5%	18 42.9%	35 41.2%
Hispanic	8 18.6%	7 16.7%	15 17.6%
Other	0 0%	1 2.4%	1 1.2%
Region of Enrollment (Count of Participants)
United States	43 100%	42 100%	85 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Umbilical cord blood specimen only available for 70 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	33	37
Median (Inter-Quartile Range) [ng/mL]	1.02	1.09

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Umbilical Cord Blood Cortisol
Description	Cortisol level (ug/mL) as measure of fetal immune suppression
Time Frame	At delivery

Outcome Measure Data

Analysis Population Description

Umbilical cord blood specimen only available for 70 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	33	37
Median (Inter-Quartile Range) [ug/mL]	2.0	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Umbilical Insulin-Like Growth Factor 1
Description	Insulin-like growth factor 1 level (ng/mL) as a measure of in utero metabolic status
Time Frame	At delivery

Outcome Measure Data

Analysis Population Description

Umbilical cord blood specimen only available for 71 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	33	38
Median (Inter-Quartile Range) [ng/mL]	78	58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Umbilical Cord Blood Leptin
Description	Leptin level (ng/mL) as measure of fetal adiposity
Time Frame	At delivery

Outcome Measure Data

Analysis Population Description

Umbilical cord blood specimen only available for 71 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	33	38
Median (Inter-Quartile Range) [ng/mL]	7.5	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Neonatal Hypoglycemia
Description	Number of neonates with capillary blood glucose < 40 mg/dL
Time Frame	After birth, up to 48 hours of life

Outcome Measure Data

Analysis Population Description

Glucose only available for 82 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	41	41
Count of Participants [Participants]	20 46.5%	21 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Neonatal Hypoglycemia Treatment
Description	Number of neonates with hypoglycemia requiring treatment with dextrose gel or dextrose intravenous fluids
Time Frame	After birth, during hospital admission, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

Glucose only available for 82 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	41	41
Count of Participants [Participants]	9 20.9%	8 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Neonatal Glucose Nadir
Description	Lowest neonatal capillary blood glucose (mg/dL)
Time Frame	After birth, during hospital admission, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

Glucose only available on 82 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	41	41
Mean (Standard Deviation) [mg/dL]	42.3 (2.9)	42.2 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Timing of Neonatal Blood Glucose Nadir
Description	Number of hours after birth when lowest neonatal capillary blood glucose was measured
Time Frame	After birth, during hospital admission, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

Glucose only available on 82 neonates

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	41	41
Median (Inter-Quartile Range) [hours]	1.7	1.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Neonatal Intensive Care Unit Admission
Description	Number of neonates admitted to the neonatal intensive care unit for > 24 hours
Time Frame	Date of delivery to date of discharge from hospital, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	43	42
Count of Participants [Participants]	15 34.9%	21 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	Neonatal Intensive Care Unit Length of Stay
Description	Number of days of neonatal intensive care unit stay
Time Frame	From neonatal intensive care unit admission to discharge, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	43	42
Median (Inter-Quartile Range) [days]	6	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neonates Born to Mothers Receiving Intervention, Neonates Born to Mothers Receiving Usual Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Neonatal Seizures
Description	Number of neonates who had seizures
Time Frame	After birth, during hospital admission, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	43	42
Count of Participants [Participants]	0 0%	0 0%

12. Secondary Outcome

Title	Neonatal Mortality
Description	Number of neonates who died
Time Frame	After birth, during hospital admission, assessed up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neonates Born to Mothers Receiving Intervention	Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Neonates born to mothers who received intervention	Neonates born to mothers who received usual care
Measure Participants	43	42
Count of Participants [Participants]	0 0%	0 0%

13. Secondary Outcome

Title	Maternal Hyperglycemia
Description	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
Time Frame	For five days after first dose of betamethasone administration

Outcome Measure Data

Analysis Population Description

Only 39 participants in the intervention group had at least one capillary blood glucose measured

Arm/Group Title	Mothers: Intervention	Mothers: Usual Care
Arm/Group Description	Mothers 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.	Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.
Measure Participants	39	0
Count of Participants [Participants]	32 74.4%	0 0%

14. Secondary Outcome

Title	Maternal Insulin Treatment
Description	Number of mothers who received insulin for treatment of hyperglycemia
Time Frame	For five days after first dose of betamethasone administration

Outcome Measure Data

Analysis Population Description

Only 39 mothers in the intervention group had at least one capillary blood glucose measured

Arm/Group Title	Mothers: Intervention	Mothers: Usual Care
Arm/Group Description	Mothers 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.	Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.
Measure Participants	39	0
Count of Participants [Participants]	22 51.2%

15. Secondary Outcome

Title	Maternal Hypoglycemia
Description	Number of mothers with capillary blood glucose <60 mg/dL
Time Frame	For five days after first dose of betamethasone administration

Outcome Measure Data

Analysis Population Description

Only 39 mothers in the intervention group had at least one capillary blood glucose measured

Arm/Group Title	Mothers: Intervention	Mothers: Usual Care
Arm/Group Description	Mothers 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.	Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.
Measure Participants	39	0
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Collected for mothers from the time of informed consent until delivery or hospital discharge for a maximum of 5 days. For neonates, AEs were collected from the time of birth until discharge or 28 days of life.
Arm/Group Title	Mothers: Intervention		Mothers: Usual Care		Neonates Born to Mothers Receiving Intervention		Neonates Born to Mothers Receiving Usual Care
Arm/Group Description	Mothers 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.		Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.		Neonates born to mothers who received intervention		Neonates born to mothers who received usual care
All Cause Mortality
	Mothers: Intervention		Mothers: Usual Care		Neonates Born to Mothers Receiving Intervention		Neonates Born to Mothers Receiving Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/42 (0%)		0/43 (0%)		0/42 (0%)
Serious Adverse Events
	Mothers: Intervention		Mothers: Usual Care		Neonates Born to Mothers Receiving Intervention		Neonates Born to Mothers Receiving Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/42 (0%)		0/43 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Mothers: Intervention		Mothers: Usual Care		Neonates Born to Mothers Receiving Intervention		Neonates Born to Mothers Receiving Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/44 (25%)		7/42 (16.7%)		30/43 (69.8%)		35/42 (83.3%)
Endocrine disorders
Neonatal Hypoglycemia	0/0 (NaN)	0	0/0 (NaN)	0	20/43 (46.5%)	20	21/42 (50%)	21
General disorders
Neonatal Intensive Care Unit Admission	0/0 (NaN)	0	0/0 (NaN)	0	15/43 (34.9%)	15	21/42 (50%)	21
Hepatobiliary disorders
Neonatal Hyperbilirubinemia	0/0 (NaN)	0	0/0 (NaN)	0	10/43 (23.3%)	10	18/42 (42.9%)	18
Reproductive system and breast disorders
Cesarean delivery	11/43 (25.6%)	11	7/42 (16.7%)	7	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Neonatal Respiratory Distress Syndrome	0/0 (NaN)	0	0/0 (NaN)	0	6/43 (14%)	6	4/42 (9.5%)	4
Transient Tachypnea of the Newborn	0/0 (NaN)	0	0/0 (NaN)	0	3/43 (7%)	3	2/42 (4.8%)	2
Neonatal Apnea	0/0 (NaN)	0	0/0 (NaN)	0	2/43 (4.7%)	2	4/42 (9.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.