What are the risks to the fetus of a pregnant patient with Graves' disease and how can they be managed?

Fetal Complications of Graves' Disease in Pregnancy

Graves' disease in pregnancy poses significant risks to the fetus including thyrotoxicosis, hypothyroidism, growth restriction, preterm birth, stillbirth, and congenital malformations—all of which can be mitigated through proper maternal treatment with thioamide medications while maintaining maternal free T4 in the high-normal range. 1, 2

Direct Fetal Thyroid Dysfunction

Fetal and Neonatal Thyrotoxicosis

• Maternal thyrotropin receptor antibodies (TRAb) cross the placenta and directly stimulate the fetal thyroid, causing fetal hyperthyroidism even when the mother is adequately treated or previously ablated. 2, 3
• Elevated maternal TRAb levels (particularly >200 IU/L) in the third trimester are a major risk factor requiring fetal thyroid ultrasound monitoring, regardless of maternal thyroid status. 2, 3
• Fetal thyrotoxicosis manifests as tachycardia, growth restriction, advanced bone age, goiter, and hydrops fetalis on ultrasound. 3
• Neonatal thyrotoxicosis can emerge in the first few days after birth once maternal antithyroid drugs clear from the infant's system, persisting for several months until maternal antibodies are metabolized. 3

Fetal Hypothyroidism

• Excessive maternal antithyroid drug therapy can suppress fetal thyroid function, causing fetal goiter and cretinism. 4, 5
• This risk necessitates using the lowest possible thioamide dose to maintain maternal free T4 in the high-normal range rather than targeting complete normalization. 1, 2
• Fetal thyroid suppression from maternal treatment is usually transient and rarely requires intervention, making the benefits of maternal treatment outweigh this risk. 2

Pregnancy Complications and Adverse Outcomes

Maternal Hyperthyroidism-Related Fetal Risks

• Untreated or inadequately controlled maternal hyperthyroidism significantly increases risks of spontaneous abortion, preterm delivery, stillbirth, and intrauterine growth restriction. 1, 5, 6
• Severe preeclampsia risk is elevated in pregnant women with poorly controlled Graves' disease. 1
• Maternal heart failure from uncontrolled thyrotoxicosis further compromises fetal oxygenation and outcomes. 5

Congenital Malformations

• Methimazole exposure during the first trimester carries a risk of specific congenital malformations including aplasia cutis, choanal atresia, and esophageal atresia. 1, 4
• This risk makes propylthiouracil (PTU) the preferred first-trimester agent despite its hepatotoxicity risk. 1, 5
• Switching from PTU to methimazole after the first trimester is recommended to minimize maternal hepatotoxicity while avoiding the critical organogenesis period. 1

Management Strategy to Minimize Fetal Risk

Medication Selection and Monitoring

• Use PTU during the first trimester (weeks 0-13) to avoid methimazole-associated birth defects. 1
• Switch to methimazole for the second and third trimesters due to PTU's severe maternal hepatotoxicity risk. 1, 5
• Target maternal free T4 in the high-normal range using the lowest effective thioamide dose—this balances preventing maternal complications while minimizing fetal thyroid suppression. 1, 2
• Monitor maternal thyroid function every 2-4 weeks initially, then each trimester. 2

Fetal Surveillance

• Measure maternal TRAb levels; if elevated (especially >200 IU/L), perform serial fetal ultrasounds to assess for thyroid enlargement, growth, heart rate, and hydrops. 2, 3
• Fetal tachycardia (>160-170 bpm sustained), goiter, or growth restriction warrant consideration of adjusting maternal antithyroid medication. 3
• Even women with prior thyroid ablation (radioactive iodine or surgery) who have persistent TRAb require fetal monitoring as antibodies can still affect the fetus. 2, 3

Delivery and Neonatal Management

• Inform the neonatal team about maternal Graves' disease and TRAb status before delivery to prepare for potential neonatal thyroid dysfunction. 2
• Measure cord blood TSH and free T4 at delivery in all infants born to mothers with active Graves' disease or elevated TRAb. 3
• Neonatal thyrotoxicosis may not manifest immediately—monitor for several days to weeks as maternal antithyroid drugs clear. 3
• Neonatal hyperthyroidism typically resolves within 2-3 months as maternal antibodies are metabolized, but requires treatment with antithyroid drugs and supportive care during this period. 3, 7

Critical Pitfalls to Avoid

• Never use radioactive iodine (I-131) during pregnancy—it is absolutely contraindicated and will ablate the fetal thyroid. 1
• Do not overtarget maternal thyroid normalization; keeping free T4 in the high-normal range prevents fetal hypothyroidism from excessive medication. 1, 2
• Do not assume that maternal euthyroid status eliminates fetal risk—elevated TRAb can cause fetal thyrotoxicosis independent of maternal thyroid function. 2, 3
• Do not continue PTU beyond the first trimester due to severe maternal hepatotoxicity risk including liver failure and death. 1, 5
• Do not neglect postpartum evaluation—Graves' disease commonly recurs or worsens postpartum, and neonatal thyroid dysfunction may emerge after delivery. 1, 3