How should a pregnant woman with known congenital adrenal hyperplasia due to 21‑hydroxylase deficiency be managed regarding glucocorticoid and mineralocorticoid replacement, stress dosing during illness and labor, and prenatal treatment to prevent fetal virilization?

Management of Congenital Adrenal Hyperplasia in Pregnancy

Pregnant women with established CAH due to 21-hydroxylase deficiency should continue hydrocortisone (not dexamethasone) for their own adrenal insufficiency, with dose increases of 2.5-10 mg daily during the third trimester, stress dosing of 100 mg IV hydrocortisone at labor onset (repeated every 6 hours), and fludrocortisone dose adjustments based on blood pressure and electrolytes rather than renin levels. 1

Glucocorticoid Management for the Affected Mother

Routine Pregnancy Dosing

• Hydrocortisone is the glucocorticoid of choice because it does not cross the placenta, protecting the fetus from unnecessary steroid exposure 2
• Increase the daily hydrocortisone dose by 2.5-10 mg during the third trimester to account for rising free cortisol levels and increased physiologic demand 1
• The baseline replacement remains 15-25 mg daily in divided doses (typically 10 mg + 5 mg + 2.5 mg at 07:00,12:00, and 16:00) 3

Critical Pitfall

• Never use dexamethasone to treat the pregnant woman with CAH herself - dexamethasone crosses the placenta and would expose an unaffected fetus to unnecessary glucocorticoid suppression 2

Mineralocorticoid Adjustments

• Fludrocortisone dose often requires increases during late pregnancy due to the anti-mineralocorticoid effects of rising progesterone 1
• Monitor using salt cravings, blood pressure, and serum electrolytes - not plasma renin activity, which physiologically increases during normal pregnancy and is therefore unreliable 1
• Standard fludrocortisone dosing ranges from 50-200 µg daily, though some patients may require up to 500 µg daily 3

Stress Dosing Protocols

During Labor and Delivery

• Administer 100 mg hydrocortisone IV (Solu-Cortef) at the onset of labor 1
• Repeat 100 mg IV every 6 hours if labor is prolonged 1
• After delivery, double the oral dose for 24-48 hours, then taper back to the pre-pregnancy maintenance dose 1

During Illness in Pregnancy

• Double the oral hydrocortisone dose for 24-48 hours during any acute illness to prevent adrenal crisis 3
• Patients must understand that even mild gastrointestinal upset prevents medication absorption precisely when steroid needs are highest 1

Prenatal Treatment to Prevent Fetal Virilization

When to Consider

This is a separate decision from managing the mother's CAH and applies only when:

• The fetus is at risk for inheriting CAH (both parents are carriers or affected) 4, 5
• The goal is to prevent virilization of a potentially affected female fetus 6

The Dexamethasone Protocol

• Dexamethasone 20 µg/kg/day (based on pre-pregnancy weight) must be started before 7 weeks gestation to be effective, as genital differentiation begins early 5, 6
• Dexamethasone is used because it crosses the placenta to suppress fetal adrenal androgen production 2, 7
• Treatment continues until fetal sex and CAH status are determined via chorionic villus sampling (10-12 weeks) or amniocentesis (15-18 weeks) 4, 5
• Only 1 in 8 fetuses (affected females) actually benefits - the other 7 (males and unaffected females) receive unnecessary first-trimester steroid exposure 5

Major Controversy and Caution

• Prenatal dexamethasone treatment remains controversial due to limited long-term safety data and the exposure of mostly unaffected fetuses 5, 6
• This intervention should only be undertaken in experienced centers or as part of research protocols after extensive counseling about risks and benefits 5
• Short-term studies suggest safety for mother and fetus, but long-term neurodevelopmental data remain preliminary 6

Preconception Optimization

• Women with classic CAH should optimize glucocorticoid treatment before attempting conception to reduce flare risk 4
• Achieving biochemical remission for 1 year prior to conception reduces the 38% maternal complication rate and the risk of disease flares during pregnancy 1
• Preconception genetic counseling with a high-risk obstetrics specialist is recommended given the autosomal recessive inheritance pattern 4

Monitoring During Pregnancy

• Monitor for signs of adrenal crisis throughout pregnancy, particularly during intercurrent illness 4
• Assess for pregnancy complications including gestational diabetes, hypertension, and chorioamnionitis, which occur at higher rates 4
• Flares are 3 times more common postpartum than during pregnancy, requiring close monitoring for the first 6 months after delivery 1

Postpartum Management

• Continue doubled oral hydrocortisone dose for 24-48 hours after delivery, then taper to pre-pregnancy maintenance 1
• Resume standard fludrocortisone dosing as progesterone levels fall 1
• Intensify monitoring during the first 6 months postpartum when disease flares are most likely 1