What are the management recommendations for a pregnant patient with neurofibromatosis (NF)?

Management of Pregnancy in Neurofibromatosis Type 1

Pregnant women with NF1 should be referred to a high-risk obstetrician for multidisciplinary management, as these pregnancies carry significantly elevated risks of maternal complications (including life-threatening vascular events and pheochromocytoma), fetal complications (20.7% first-trimester loss, 8.7% stillbirth, 13-46% intrauterine growth restriction), and require specialized anesthesia planning. 1, 2, 3, 4

Preconception and Early Pregnancy Counseling

Genetic Counseling

• Educate patients that NF1 follows autosomal dominant inheritance with 50% offspring recurrence risk for each pregnancy 1, 5
• Discuss availability of preimplantation genetic diagnosis (PGD) and prenatal diagnosis via chorionic villus sampling or amniocentesis for known disease-causing NF1 mutations 1, 2
• Note that individuals with de novo mutations, somatic mosaicism, and large genomic rearrangements have technical limitations for PGD 1

Contraception Planning

• If pregnancy is not desired, standard oral estrogen-progestogen or pure progestogen contraceptives are safe, with 89% showing no associated neurofibroma growth 6
• Avoid high-dose depot progesterone formulations, as 3% of women experience significant tumor growth with these preparations 6

Preconception and First Trimester Assessment

Baseline Maternal Evaluation

• Document extent of disease with baseline MRI of known or suspected non-superficial plexiform neurofibromas to establish size and characteristics for comparison if symptoms develop during pregnancy 1, 5, 2
• Screen for pheochromocytoma (particularly critical before pregnancy): assess for paroxysmal hypertension, headache, palpitations, and diaphoresis 5, 7
• Measure blood pressure at every visit, as hypertensive complications including pre-eclampsia and pheochromocytoma occur at higher rates 7, 2
• Evaluate cardiovascular status, as vascular rupture and cardiorespiratory complications can be life-threatening 2, 8

Critical Warning Signs Requiring Immediate Evaluation

• Progressive severe pain, rapid tumor growth, or new unexplained neurologic symptoms mandate urgent imaging to rule out malignant peripheral nerve sheath tumor (MPNST), which can be fatal during pregnancy 5, 7, 8
• The risk of MPNST transformation is 8-13% for plexiform neurofibromas, with mortality risk if unrecognized 7, 8

Ongoing Pregnancy Management

Antenatal Surveillance

• Provide close antenatal observation at a high-risk tertiary center with multidisciplinary team including maternal-fetal medicine, medical genetics, neurology, and anesthesiology 2, 4
• Monitor for intrauterine growth restriction with serial ultrasounds, as rates range from 13-46% in NF1 pregnancies 3, 4
• Assess for preterm delivery risk, as mean gestational age at delivery is significantly lower (36.8 vs. 39.2 weeks in controls) 4
• Evaluate for rapidly enlarging masses throughout pregnancy, as hormonal changes can accelerate neurofibroma growth 2, 8

Specific Maternal Complications to Monitor

• Screen systematically for pheochromocytoma symptoms at each visit, as intraoperative hypertensive crises can occur if undiagnosed 7, 2
• Assess for pre-eclampsia development, which occurs at higher rates in NF1 pregnancies 2
• Monitor for vascular complications and cardiorespiratory issues, which can be life-threatening 2, 8
• Continue assessment for depression, chronic pain, and neuropathy throughout pregnancy 5, 6

Delivery Planning and Anesthesia

Preanesthesia Assessment

• Preanesthesia neuraxial imaging to evaluate for spinal or paraspinal neurofibromas is probably not needed for routine epidural or spinal anesthesia 1, 7
• If concerns exist about spinal neurofibromas, spinal anesthesia may be considered over epidural 1, 7
• No significant adverse events have been reported for women with NF1 undergoing epidural anesthesia 7
• Perform imaging before delivery if large neurofibromas affect the face, neck, upper spine, or airways, as general anesthesia may be challenging 2

Mode of Delivery Considerations

• Cesarean section rates are elevated (26-38.5%) in NF1 pregnancies due to anatomical considerations and fetal complications 3, 4
• Assess for large neurofibromas at the level of planned skin incision or birth canal that may complicate vaginal or cesarean delivery 2
• Anticipate potential uterine atony if uterine lesions are present 2

Postpartum Management

Immediate Postpartum Care

• Plan multimodal analgesia, as chronic pain affects the majority of NF1 adults and baseline pain may be elevated 7
• Continue careful surveillance postpartum, as some complications can develop after delivery 2

Ongoing Follow-up

• Resume annual surveillance including blood pressure monitoring, assessment for tumor changes, and screening for MPNST warning signs 5, 6
• Coordinate ongoing care through specialized NF1 clinic for long-term management 1, 5

Common Pitfalls to Avoid

• Do not dismiss new or worsening pain during pregnancy as normal pregnancy discomfort—this may signal MPNST transformation requiring urgent evaluation 5, 8
• Do not assume routine anesthesia protocols without anesthesiology consultation, as anatomical variations require individualized planning 7, 2
• Do not underestimate first-trimester loss risk (20.7%) and stillbirth risk (8.7%) when counseling patients 3, 4
• Do not delay referral to high-risk obstetrics—early multidisciplinary involvement improves outcomes 1, 2, 4