Abstract

Background and Objectives: Graves disease complicates 0.2% of pregnancies. Maternal thyrotoxicosis increases morbidity in both fetus and mother. The main objective of this study was to evaluate the clinical outcomes in neonates born to mother with Graves disease at birth and first postnatal month and correlate maternal and neonatal Thyrotropin receptor antibody (TRAb) levels and outcomes. This is the first study in India studying the neonatal outcomes in large cohort of pregnant women with Graves disease. Methods: The study was conducted in a 3000 bedded tertiary care centre in South Tamilnadu over a period of two years. 46 pregnant women with Graves disease who were TRAb positive at third trimester were evaluated with serial thyroid function tests (TFTs). Neonates born to these mothers were evaluated for signs of hyperthyroidism, hypothyroidism, and adverse effect of antithyroid drugs. TFTs and TRAb levels were measured at day 3 of postnatal life and after one month. TFTS and TRAb levels were measured using electro chemiluminescenceimmunoassay (ECLIA) by Roche cobas e411. Results: Out of 46 TRAb positive pregnant women 22 (47%) had TRAb levels more than 3 times in the 3rd trimester and all neonates born to these mothers were TRAb positive (100%). Five women had very high TRAb levels (>10 times), among which 4 (80%) presented with thyroid storm andwereassociatedadverse pregnancy outcomes, 3 had intrauterine death, 1 had abortionand1 with still birth. Of the 41 (89%) women who delivered, 6 were preterm delivery (14%). Out of 41 neonates, 19 (46%) were TRAb positive at day3 of life. TRAb levels normalized by 3-6 months (Mean -150 days) in all neonates. One fetus hadfetal thyrotoxicosis diagnosed by goitre and fetal tachycardiain antenatal ultrasound which improved with treatment in the mother. Out of 19 Trab positive neonates, 4 neonates (21%) had transient neonatal thyrotoxicosis. However, all were asymptomatic, did not require treatment and spontaneously became euthyroid with negative TRAbtitres by3-6 months.5 neonates (26%) had transient hypothyroidismpossibly because of TRAb induced blocking antibodies requiring thyroxine therapyfor 6 months. Thyroxine was stopped onceTRAbtitres became negative. 2 neonates (10%) had transient central hypothyroidism because of transient suppression of pituitary axis by high maternal thyroid hormone levels requiring thyroxine therapyand the axis recovered by 6 months. 1 neonate developed bilateral cleft lip and palate probably due to inadvertent use of high dose of antithyroid drugs in I trimester. Also 5 neonates developed transient drug induced hypothyroidism which resolved by 15 days of life. Conclusion: More than 3 times the TRAb levels in mother wastransmitted to the infants, which was transient and spontaneously resolved by 3-6 months. Few TRAb positive infants (57%) was associated with transient neonatal thyrotoxicosis, transient neonatal hypothyroidism and transient central hypothyroisim which may require followup and close observation. Uncontrolled hyperthyroidism with high TRAb (>10 times)) were associated with poor pregnancy outcomes and all had fetal demise. Thus TRAb levels in mother may predict pregnancy outcomes and in newborn help in vigilant interpretation of abnormal TFTs and helpto avoid inadvertent Thyroxine/ antithyroid drugs.

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