What maternal and fetal complications should be expected in a pregnant woman with congenital adrenal hyperplasia (21‑hydroxylase deficiency) and how should they be monitored?

Pregnancy Risks in Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

Women with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency face decreased fertility but can achieve successful pregnancies with careful glucocorticoid management and high-risk obstetric monitoring, though they remain at elevated risk for gestational diabetes, hypertension, chorioamnionitis, cesarean delivery, and delivering small-for-gestational-age infants. 1

Maternal Complications

Metabolic and Endocrine Risks

• Gestational diabetes mellitus occurs at increased frequency due to chronic glucocorticoid therapy required for adrenal suppression throughout pregnancy. 1
• Maternal hypertension develops more commonly than in the general obstetric population, requiring blood pressure targets of 110-140/80-85 mmHg with safe antihypertensives (methyldopa, labetalol, or long-acting nifedipine). 2
• Adrenal crisis represents a life-threatening complication if glucocorticoid dosing is inadequate during labor, delivery, or postpartum stress states. 1

Obstetric Complications

• Chorioamnionitis rates are elevated in pregnant women with CAH, necessitating vigilant monitoring for signs of intrauterine infection. 1
• Cesarean section is performed more frequently, though vaginal delivery with epidural analgesia and elective instrumental assistance remains the preferred approach when maternal and fetal status permit. 2
• Preeclampsia risk is heightened and requires screening at every prenatal visit with urinalysis, blood pressure assessment, and laboratory panels (hemoglobin, platelets, liver enzymes, uric acid, creatinine) at ≥28 weeks and ≥34 weeks gestation. 2

Fetal and Neonatal Complications

Growth and Development

• Small-for-gestational-age infants are born more frequently to mothers with CAH, requiring serial fetal ultrasound beginning at 26 weeks gestation and repeated every 2-4 weeks if biometry remains normal. 2, 1
• Prematurity occurs at increased rates, particularly when maternal disease is poorly controlled or complications such as preeclampsia develop. 2

Virilization Risk (Female Fetuses)

• Female fetuses are NOT at risk for virilization from maternal hyperandrogenism because placental aromatase efficiently converts maternal androgens to estrogens, protecting the fetus even when maternal androgen levels are markedly elevated. 3
• This protective mechanism remains effective regardless of maternal serum androgen concentrations during pregnancy. 3

Glucocorticoid Management Algorithm

Preconception Optimization

• Optimize glucocorticoid dosing before conception to achieve adequate adrenal suppression while minimizing metabolic side effects; baseline assessment should document serum creatinine and proteinuria. 2, 1

During Pregnancy

• Continue maintenance glucocorticoid therapy throughout gestation with dose adjustments based on clinical status and biochemical monitoring (17-hydroxyprogesterone, androstenedione, testosterone). 1, 3
• Increase glucocorticoid dose during labor and delivery to stress-dose levels (typically hydrocortisone 100 mg IV every 8 hours or equivalent) to prevent adrenal crisis. 1
• Monitor maternal androgen levels serially to ensure adequate suppression, though even elevated levels do not threaten female fetal virilization due to placental aromatization. 3

Postpartum

• Rapidly taper glucocorticoids to pre-pregnancy maintenance doses within 24-48 hours after delivery to avoid prolonged supraphysiologic exposure. 1
• Monitor closely for adrenal insufficiency during the postpartum period, particularly during breastfeeding or intercurrent illness. 1

Monitoring Protocol

Maternal Surveillance

• Monthly assessment of blood pressure, weight, glucose tolerance, and electrolytes throughout pregnancy, with intensified frequency if hypertension or proteinuria develops. 2
• Screen for gestational diabetes at 24-28 weeks gestation with 75-gram oral glucose tolerance test, given the elevated risk from chronic glucocorticoid therapy. 2
• Assess for superimposed preeclampsia at every prenatal visit using blood pressure measurement, urinalysis for proteinuria, and symptom review (headache, visual changes, right upper quadrant pain). 2

Fetal Surveillance

• Initiate fetal ultrasound at 26 weeks to assess growth, amniotic fluid volume, and placental function, then repeat every 2-4 weeks if normal. 2
• Increase ultrasound frequency to weekly or twice-weekly when fetal growth restriction is suspected or maternal uric acid is elevated. 2
• Perform fetal echocardiography when either parent has CAH to screen for congenital heart disease, as offspring have increased CHD risk. 4

Preconception Counseling Essentials

Genetic Considerations

• Autosomal recessive inheritance confers a 25% recurrence risk for affected offspring when both parents are carriers; preconception genetic testing and counseling with a high-risk obstetrics specialist is mandatory. 1
• In vitro fertilization with preimplantation genetic testing can be offered to couples wishing to avoid having a child with CAH. 1

Fertility Optimization

• Optimize glucocorticoid therapy first, followed by ovulation induction medications (clomiphene citrate) and gonadotropins if spontaneous conception does not occur, as women with classic CAH have decreased baseline fecundity. 1

Critical Pitfalls to Avoid

• Never discontinue glucocorticoids during pregnancy, as this precipitates maternal adrenal crisis and uncontrolled hyperandrogenism. 1
• Never use ACE inhibitors or ARBs for hypertension management, as these cause fetal renal dysgenesis and are absolutely contraindicated throughout pregnancy. 2
• Never delay stress-dose glucocorticoids during labor, delivery, or surgical procedures, as inadequate coverage leads to life-threatening adrenal crisis. 1
• Never assume elevated maternal androgens will virilize a female fetus, as placental aromatase provides complete protection regardless of maternal androgen levels. 3

Delivery Planning

• Target delivery at 39 weeks when maternal disease is well-controlled and fetal monitoring is reassuring, with earlier delivery indicated for worsening maternal status or fetal distress. 2
• Administer stress-dose hydrocortisone (100 mg IV every 8 hours) beginning at the onset of labor or before scheduled cesarean section, continuing until 24-48 hours postpartum. 1
• Prefer vaginal delivery with epidural analgesia over cesarean section when obstetric factors permit, as this reduces maternal morbidity. 2