What are the implications of Porphyria (a group of disorders that result from a buildup of natural chemicals that produce porphyrin) in pregnancy?

From the Guidelines

Pregnant women with porphyria require meticulous management to minimize risks to both mother and baby, and should be managed by a multidisciplinary team including obstetricians, hematologists, and genetic counselors. The implications of porphyria in pregnancy are significant, and can be associated with increased risks of complications such as hypertension and pre-eclampsia [ 1 ].

Key Considerations

• Preventive measures are crucial to avoid triggering acute attacks, and include avoiding known attack triggers such as certain medications (barbiturates, sulfonamides, estrogens), fasting, stress, and infections.
• During acute attacks, treatment may include intravenous hemin at 3-4 mg/kg daily for 3-4 days, along with adequate carbohydrate intake and glucose infusions if needed.
• Pain management should use safe medications like acetaminophen and opioids if necessary, while avoiding porphyrinogenic drugs.
• For cutaneous porphyrias, sun protection is essential, and beta-carotene may be used in some cases.
• Regular monitoring of liver function, renal function, and blood pressure is important as porphyria can be associated with hypertension and pre-eclampsia.

Special Considerations

• Phototherapy should be used with caution in infants with cholestatic jaundice, as it may cause a dark, grayish-brown discoloration of the skin, serum, and urine (the bronze infant syndrome) [ 1 ].
• Congenital porphyria or a family history of porphyria is an absolute contraindication to the use of phototherapy, as is the concomitant use of drugs or agents that are photosensitizers [ 1 ].
• Genetic counseling should be offered as porphyrias are hereditary conditions.

Management and Treatment

• A multidisciplinary team approach is essential to ensure the safe management of pregnant women with porphyria, and should include regular monitoring and prompt treatment of any complications that may arise.
• Labor and delivery generally proceed normally, but careful medication selection for anesthesia and postpartum care is crucial to prevent triggering attacks.

From the FDA Drug Label

About 50% of the women with acute intermittent porphyria experience an acute attack of porphyria in pregnancy and/or the puerperium. It is most severe in early pregnancy and the puerperium, and can result in fatal outcome Although anecdotal evidence suggests safe use of hematin during pregnancy, the available human data is not sufficient to establish the presence or absence of drug-associated risk. Animal reproduction studies have not been conducted with hematin. It is also not known whether hematin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity PANHEMATIN should be given to a pregnant woman only if clearly needed. Avoid administering hematin in severe pre-eclampsia because of a theoretical risk of potentiation of the coagulation disorder

The implications of Porphyria in pregnancy are:

• Increased risk of acute attacks: About 50% of women with acute intermittent porphyria experience an acute attack during pregnancy and/or the puerperium.
• Severe outcomes: Acute attacks can be severe and result in fatal outcomes, especially in early pregnancy and the puerperium.
• Uncertain safety of hematin: Although anecdotal evidence suggests safe use of hematin during pregnancy, there is limited human data to establish the presence or absence of drug-associated risk.
• Precautions: Hematin should be given to pregnant women only if clearly needed, and avoided in severe pre-eclampsia due to a theoretical risk of potentiation of the coagulation disorder 2 2.

From the Research

Implications of Porphyria in Pregnancy

The implications of porphyria in pregnancy are significant and can lead to various complications for both the mother and the fetus. Some of the key implications include:

• Higher rates of spontaneous abortion, hypertension, and low birth weight infants 3
• Considerable mortality rates, ranging from 2-42% 3
• Increased risk of acute attacks, especially during the first trimester 3, 4
• Misdiagnosis of porphyria, which can lead to inappropriate treatment and poor outcomes 3

Clinical Manifestations and Treatment

The clinical manifestations of porphyria in pregnancy can vary, but may include abdominal pain, neurological symptoms, and psychiatric disturbances 4, 5. Treatment options for porphyria in pregnancy include:

• Symptomatic treatment, such as analgesics and neuroleptics 3, 5
• Glucose infusion, which can help alleviate symptoms 5
• Hemin or heme-arginate therapy, which can be safely administered during pregnancy 3, 6
• Arginine hemoglobin, calcium gluconate, and sodium chloride, which may be used to treat posterior reversible encephalopathy syndrome (PRES) 6

Maternal and Fetal Outcomes

With proper management and treatment, women with porphyria can have successful pregnancies and healthy outcomes for both mother and fetus 7, 4, 6. However, close monitoring and involvement of porphyria specialists are recommended to reduce the risk of complications and improve outcomes 7. Some studies have reported increased levels of heme precursors during pregnancy, but this does not necessarily lead to a higher frequency of clinical porphyria manifestations 7.