Babies born to mothers with thyroid disease

Abstract

Thyroid dysfunctions are the second most common endocrine disorders complicating pregnancy after diabetes mellitus. Maternal thyroid dysfunctions are associated with miscarriage, preeclampsia, eclampsia, placental abruption and preterm delivery. As maternal thyroxine is essential for fetal neurodevelopment, until the foetal thyroid gland starts to produce thyroid hormones in the second trimester of gestation, reduced availability of maternal thyroid hormones may impair neurogical development of the foetus. It has been reported decreased IQ in infants born to mothers with hypothyroidism or hypothyroxinemia. Maternal hypothyroidism, defined as an elevated TSH level with a decreased (overt) or normal (subclinical) levels of circulating free T4, is common during pregnancy with a prevalence ranging from 0.5% (overt) to 2.5% (subclinical). Serum TSH levels, using trimesterspecific reference ranges (first trimester <2.5 mIU/ml, second and third trimester <3 mIU/ml), is a reliable test of maternal thyroid function in pregnancy. As untreated overt hypothyroidism during pregnancy has been shown to be associated with an increased risk of miscarriage, preterm birth, low birth weight and impaired fetal neurocognitive development, treatment during pregnancy is mandatory. Treatment of subclinical hypothyroidism during pregnancy is not universally recommended however a recent paper by Negro et al. has shown that treatment reduces the occurrence of adverse outcomes in the mother and fetus. The most common etiology of maternal hypothyroidism is Hashimoto’s thyroiditis; other causes include prior treatment for hyperthyroidism (radioactive iodine or thyroidectomy) and iodine deficiency. The mother with Hashimoto’s thyroiditis may have TSH receptor blocking or rarely stimulating antibodies (TRab) causing transient neonatal hypo or hyperthyroidism. Maternal high TRab titres are associated to an higher risk of hypo /or hyperthyroidism but the antibody titre does not discriminate blocking from stimulating antibodies that may also be present at the same time. If maternal TRab titre is elevated or unknown cord blood should be evaluated at birth for TRab, FT4 and TSH levels. A physical examination (heart rate and presence of goitre) should always be performed. In case of elevated TRab titre, the newborn must be checked at 10–14 days of age for clinical signs of hypo or hyperthyroidism and TSH and FT4 levels should be measured again; a treatment with tiroxine (10 mcg/kg/day) should be considered in case of elevated TSH and reduced FT4 levels. If no TRab are detectable on maternal blood or if the maternal hypothyroidism is due to a congenital cause (aplasia or hypoplasia of the thyroid gland) the evaluation of TSH on filter paper at 3–4 days of life should suffice. However babies born to mothers with autoimmune thyroiditis may develop persistent hyperthyrotropinemia requiring thyroid hormone replacement therapy even if no TRab are detectable and TSH levels are normal at 3–4 days of life; in these cases a retesting of TSH levels on filter paper at 3–4 weeks of life is indicated. If maternal hypothyroidism is due to pre-pregnancy treatment for Graves’ disease (radioiodine, surgery) the newborn is at risk of neonatal thyrotoxicosis if maternal TRab are present. Overt maternal hyperthyroidism occurs in approximately 0.2– 0.4% of pregnancies and is defined as a serum TSH level below the trimester-specific reference range with elevated levels of free T4 and T3. As untreated overt hyperthyroidism during pregnancy has been shown to be associated with miscarriage, pre-eclampsia, preterm birth, fetal growth restriction and increased perinatal morbidity and mortality, treatment during pregnancy is mandatory. Subclinical maternal hyperthyroidism (reduced TSH levels with normal levels of free T4 and T3) is not associated with an increased risk of adverse events in the mother and the fetus, and treatment during pregnancy is not recommended. The most common etiology is Graves’ disease; other causes include gestational transient thyrotoxicosis, toxic adenoma, thyroiditis or excessive hormone intake. Neonatal Thyrotoxicosis due to maternal Grave’s disease is caused by the transplacental passage of thyroid stimulating antibody (TRab) present in mothers with Graves’ disease. Consequentely in babies born to mothers with active or inactive hyperthyroidism or family history of activating mutations of TSH receptor (rare), FT4, TSH and TRab levels should be evaluated on cord blood at birth; a physical examination for signs of thyrotoxicosis and presence of goitre should also be performed. Newborns are at high risk of neonatal thyrotoxicosis if the mother has clinical thyrotoxicosis requiring thionamide in the third trimester, has raised TRab during pregnancy, not assessed TRab, family history of TSH receptor mutation or evidence of fetal thyrotoxicosis. High risk newborns should be kept in hospital and observed checking again FT4 and TSH levels at 2–3 days of life; if the baby if well without signs of thyrotoxicosis he/she can be discharged even with pending results. Repeat the physical examination checking again