Antenatal Corticosteroids (ACS) for Gestational Diabetes Planned for Elective LSCS

Background and Rationale

• Maternal diabetes is an independent risk factor for neonatal RDS (Amiya et al., PLoS One 2016;11:e0147604), meaning the theoretical benefit of ACS is arguably greater
• ACS cause significant transient hyperglycaemia in diabetic women, which itself worsens fetal lung maturation and raises neonatal hypoglycaemia risk
• These opposing effects make the risk-benefit calculus complex and context-dependent

Why Elective LSCS is a Specific Problem

Standard ACS Dose and Duration (General Population)

Evidence for ACS Before Term Elective CS (General Population)

• ACS reduced RDS risk: RR 0.48 (95% CI 0.27-0.87)
• Reduced TTN: RR 0.43 (95% CI 0.29-0.65)
• Reduced NICU admission for respiratory morbidity: RR 0.42 (95% CI 0.22-0.79)
• NICU length of stay reduced by ~2.7 days
• Evidence quality: low - no reduction in mechanical ventilation or perinatal death shown

• ACS probably reduce neonatal special care admissions for respiratory complications: RR 0.45 (95% CI 0.22-0.90; moderate certainty)
• RDS reduction was uncertain (RR 0.34, 95% CI 0.07-1.65; low certainty)
• 3 of the 4 previous trials were removed due to concerns about data integrity

Evidence Specific to GDM / Elective CS

The PRECeDe Pilot Trial (PMID 37186126 - Said et al., BJOG 2023)

• Design: Triple-blind, placebo-controlled pilot RCT at a single Australian tertiary centre
• Population: Women with PGDM (T1DM, T2DM) or GDM booked for planned CS at 35+0 to 38+6 weeks
• Intervention: Betamethasone 11.4 mg IM × 2 doses, 24 hours apart, within 7 days before CS vs normal saline placebo
• Result: Of 537 eligible women, 182 approached, 47 (26%) recruited - 22 betamethasone, 25 placebo
• Conclusion: A full-scale multicentre RCT is feasible; no serious adverse events
• Limitation: Pilot study - not powered to assess clinical efficacy. The low recruitment rate (26%) reflects real-world barriers including concerns about glucose management and the perceived risk-benefit balance

Paul et al., ANZJOG 2019

• Found increased rates of neonatal hypoglycaemia in GDM women who received ACS before CS at term
• Concluded the evidence was insufficient to support routine use, and that hypoglycaemia risk warranted caution
• Referenced in RCOG GTG 74 (2022) as Evidence Level 2+

Current Guideline Positions

RCOG Green-top Guideline No. 74 (2022, updated review Feb 2025)

"Diabetes should not be considered an absolute contraindication to antenatal corticosteroids for fetal lung maturation." (Evidence level 4, Grade D)

"In women with diabetes who are receiving corticosteroids, additional insulin should be given according to an agreed protocol and close monitoring should be undertaken." (Evidence level 4, Grade D)

"For women with diabetes undergoing planned caesarean birth between 37+0 and 38+6 weeks, an informed discussion should take place with the woman about the potential risks and benefits of corticosteroids."

• Recommends ACS for all women at risk of preterm birth up to 36+6 weeks, regardless of diabetes status
• For elective CS between 37+0 and 38+6 weeks in diabetic women, the guideline does not give a blanket recommendation - it mandates an individualised, informed decision rather than routine administration
• The guideline also states that more research is needed on effectiveness in women with diabetes

NICE NG3 (Diabetes in Pregnancy)

• Diabetes is not a contraindication to ACS for fetal lung maturation
• In women with insulin-treated diabetes receiving steroids, additional insulin must be given per an agreed protocol
• Does not provide separate dosing guidance for diabetes

ACOG Committee Opinion (2017 - still referenced)

• ACS strongly recommended for 24+0 to 33+6 weeks
• Single course may be considered 34+0 to 36+6 weeks (late preterm)
• For elective CS at term in general - supportive but does not have diabetes-specific recommendations

The Glycaemic Problem: ACS-Induced Hyperglycaemia in GDM

• Blood glucose begins rising within 6-12 hours of the first betamethasone dose
• Peaks at 12-24 hours after each dose, then gradually subsides
• Women with GDM experience glucose rises of 3-5 mmol/L above baseline on average
• Effect persists for approximately 5 days after the last dose (Itoh et al., Endocr J 2016;63:101-104)

1. Maternal hyperglycaemia itself impairs fetal lung maturation - partially negating the direct ACS benefit
2. Increased fetal insulin production -> neonatal hypoglycaemia post-delivery
3. Worsened maternal glycaemic control and ketoacidosis risk (especially T1DM)

Insulin Management: JBDS Guideline (Dashora et al., PMID 34811800, Diabet Med 2022)

• Increase basal and prandial insulin doses typically by 50-80% starting with the first betamethasone injection
• OR initiate a variable rate intravenous insulin infusion (VRIII)
• 6-point blood glucose monitoring (3 pre-meal + 3 post-meal)
• If glucose >7.0 or 8.0 mmol/L on 2 consecutive readings during admission, VRIII recommended
• Substrate fluid with VRIII: 0.9% NaCl + 5% glucose + 0.15% KCl (20 mmol/L) at 50 ml/hr
• After delivery: reduce VRIII and CSII rates by at least 50% immediately

Summary of Evidence Gaps and Ongoing Uncertainty

Practical Clinical Summary

1. Gestational age < 34+6 weeks (preterm LSCS): ACS is standard of care - give betamethasone 12 mg IM × 2 doses, 24 hours apart, regardless of diabetes. Manage glucose aggressively with 50-80% insulin dose escalation per JBDS protocol.
2. 35+0 to 36+6 weeks (late preterm): ACS should be offered and strongly considered (ALPS trial data supports use in general population; GDM-specific evidence lacking but risk-benefit favours use given higher RDS risk in diabetics). Same dose/regimen.
3. 37+0 to 38+6 weeks (term elective CS): No universal recommendation for GDM women. RCOG GTG 74 mandates an individualised informed discussion. Factors to weigh:
   • Likely benefit: reduced respiratory morbidity (evidence from the general population, moderate certainty)
   • Likely harm: neonatal hypoglycaemia (elevated risk in GDM+ACS, Evidence Level 2+)
   • Most guidelines defer decision to senior clinician + patient shared decision-making
4. Dose: Betamethasone 11.4-12 mg IM, two doses 24 hours apart (not dexamethasone for this indication - betamethasone was used in all key trials)
5. Timing before LSCS: Ideally give the 2nd dose 24 hours before planned LSCS and schedule CS within 7 days of completing the course (window of maximal effectiveness)
6. Glucose management: Initiate intensive BGL monitoring (6-point daily minimum) and increase insulin doses by 50-80% from first injection. Have VRIII protocol ready. Target BGL 5.0-8.0 mmol/L (JBDS pragmatic approach).

• Sotiriadis A et al. Cochrane Database Syst Rev 2021 (PMID 34935127) - Systematic review, ACS for planned CS at term
• Said JM et al. BJOG 2023 (PMID 37186126) - PRECeDe Pilot RCT in GDM/PGDM
• Dashora U et al. Diabet Med 2022 (PMID 34811800) - JBDS guideline on hyperglycaemia management
• RCOG Green-top Guideline No. 74, 2022 (partially updated Feb 2025) - RCOG GTG 74
• Amiya RM et al. PLoS One 2016;11:e0147604 - Systematic review in special populations