Does intrapartum dexamethasone (corticosteroid) cause hypoglycemia in newly born neonates?

Does Intrapartum Dexamethasone Cause Neonatal Hypoglycemia?

Yes, antenatal corticosteroids administered in the late preterm period significantly increase the risk of neonatal hypoglycemia, with the highest risk occurring when delivery happens 12-71 hours after administration. 1

Evidence from Major Guidelines

The Society for Maternal-Fetal Medicine explicitly acknowledges that neonatal hypoglycemia was more common in the betamethasone group than in the placebo group in the landmark ALPS trial. 1 However, the guidelines note important contextual factors:

• 93% of steroid-exposed neonates with hypoglycemia experienced resolution in <24 hours, suggesting the condition was mild and self-limited 1
• Infants with hypoglycemia were paradoxically less likely to have prolonged NICU stays (>3 days) than those without hypoglycemia 1
• The European Association for the Study of the Liver notes that corticosteroids require monitoring for rare risk of neonatal bradycardia, hypotension and hypoglycemia post-delivery 1

Mechanism and Timing of Risk

The mechanism involves fetal hyperinsulinemia induced by maternal hyperglycemia following corticosteroid administration:

• Betamethasone causes maternal glucose elevation, with nondiabetic women spending 73% of time above 110 mg/dL and 17% of time above 180 mg/dL in the 24-48 hours after administration 2
• This maternal hyperglycemia crosses the placenta and causes fetal hyperinsulinemia, with betamethasone exposure associated with elevated fetal C-peptide, insulin, and leptin levels 3
• Fetal insulin and C-peptide levels >90th percentile are associated with 3- to 6-fold higher odds of neonatal hypoglycemia 3

Critical Timing Window

The highest risk period for neonatal hypoglycemia is 12-71 hours after steroid administration, with peak risk at 24-47 hours:

• Delivery 12-35 hours after first betamethasone dose carries the highest risk of hypoglycemia 4
• Delivery 24-47 hours after administration shows an adjusted relative risk of 2.09 (95% CI 1.29-3.38) compared to unexposed neonates 5
• Deliveries <48 hours after first dose have significantly higher rates of both hypoglycemia and NICU admission 4

High-Risk Populations Requiring Special Consideration

The Society for Maternal-Fetal Medicine recommends against late preterm corticosteroids in pregnant patients with pregestational diabetes mellitus (GRADE 1C) due to the risk of worsening neonatal hypoglycemia. 6

Additional risk factors for hypoglycemia include:

• Increasing maternal age 4
• Cesarean delivery 4
• Delivery after onset of labor 4
• Administration during peak maternal cortisol activity (05:00-10:59), which showed 39.5% incidence of neonatal hypoglycemia versus 16.9% when given during nadir activity (23:00-04:59) 7

Clinical Management Implications

Despite the increased hypoglycemia risk, the benefits of respiratory morbidity reduction generally outweigh the risks in appropriately selected patients:

• The ALPS trial demonstrated 20% reduction in need for respiratory support (RR 0.80,95% CI 0.66-0.97) 1
• 33% reduction in severe respiratory morbidity (RR 0.67,95% CI 0.53-0.84) 1

Practical Recommendations

When administering late preterm steroids:

• Alert the neonatal team to expect an at-risk infant requiring close glucose monitoring for 24-48 hours 6
• Consider timing of administration relative to anticipated delivery, particularly avoiding the 12-71 hour window if delivery timing is predictable 4, 5
• Avoid administration during peak maternal cortisol hours (05:00-10:59) if feasible 7
• Absolutely contraindicated in pregestational diabetes due to compounded hypoglycemia risk 6
• Monitor neonatal glucose levels closely, defining hypoglycemia as <30 mg/dL in first 24 hours and <45 mg/dL thereafter 4

Important Caveat

While neonatal hypoglycemia is independently associated with developmental delays among preschool-aged children born at 32-36 weeks gestation, the hypoglycemia from late preterm steroids appears to be predominantly mild and transient, with most cases resolving within 24 hours. 1 The long-term neurodevelopmental significance of this specific steroid-induced hypoglycemia remains under investigation.