Thyroid Disease (Maternal) - Guideline for the Ascertainment of Hyperthyroidism in Infants born to Mothers with Thyroid Disease

• Introduction
• Maternal Disease Affecting The Newborn
• Clinical Signs
• Investigations

Introduction

Thyroid hormones are essential for the normal development of brain, energy metabolism and thermogenesis in newborns. The foetal thyroid gland starts functioning as early as ten weeks of gestation and by twenty weeks they start producing hormones in response to TRH and TSH¹. At birth the TSH peaks in response to cold stress and clamping of cord followed by T3 and T4 surge². The TSH levels remains high for a week and the T3 and T4 levels gradually declines over next 4 weeks.

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Maternal Disease Affecting The Newborn

The majority of maternal hypothyroidism in UK is due to

• Autoimmune thyroiditis (Hashimotos disease - autoantibodies to thyroid peroxidase and/or thyroglobulin).
• Congenital hypothyroidism and
• Treated Graves’ disease (autoantibodies to TSH receptor).

Hashimoto’s disease
Infants are at negligible risk of transient hypothyroidism due to transplacental passage of thyroid receptor antibodies. The risk is theoretical and there are no reported cases. 

Graves’ disease
Causes hyperthyroidism in the mother. Infants born to euthyroid mothers who are treated for Graves’ disease can be euthyroid or hypothyroid due to passage of antithyroid medications through the placenta, but later on can rarely become hyperthyroid due to persistent thyroid stimulating hormone³.

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Clinical Signs

Neonatal Thyrotoxicosis

• Most likely in infants of mothers with Graves disease.
• May be present at birth or delayed (particularly if the mother is on antithyroid medications). Usually present by day 10.
• High mortality (12-20%) if left untreated

The infants may show signs of

• Irritability,
• Tachycardia,
• Flushing,
• Jaundice
• Goitre.
• Thrombocytopenia
• Excessive feeding, diarrhoea

Neonatal Hypothyroidism

• Most likely as a congenital problem or
• Theoretically infants of mothers with Hashimoto’s disease.
• Often infants with congenital hypothyroidism are described as ‘good babies’ as they sleep most of the time and rarely cry.

Other signs are

• Hypotonia
• Reduced activity
• Poor feeding
• Large fontanelles especially posterior ones and
• Hoarse cry

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Investigations

1. Infants born to Mothers with autoimmune thyroiditis (Hashimoto’s)

• No investigation required.

2. Infants born to Mothers with Congenital Hypothyroidism

• Routine newborn bloodspot screening test is sufficient in these infants.
• Most maternal congenital hypothyroidism is due to sporadic thyroid gland dysgenesis. An increasing number have a genetic cause. Most of the genetic origins have autosomal recessive inheritance.

3. Infants of Mothers with hypothyroidism secondary to treated Graves disease

• These infants are at risk of hyperthyroidism if maternal antibody levels are high.
• Mothers with Graves disease and high antibody levels at 28 weeks should have been notified to our service. Details should be in the Fetal Medicine folder on ICU, LGI.
• Ascertain maternal antibody levels if known. High risk to infant is 5 times upper limit of normal (upper limit of normal for TSH Receptor Antibodies (TBII) is 1.5u/l).
• Only babies at high risk should have thyroid function tests taken as detailed below
• Send cord blood sample for thyroid function tests and chase results.
• A decision can then be made with the attending neonatal consultant (and paediatric endocrinologist if indicated) as to when TFTs need repeating.
• In those babies who go onto to develop hyperthyroidism, the cord blood can already indicate imminent hyperthyroidism (including inappropriately ‘normal’ cord blood TSH), in which case bloods will need repeating within 1 or 2 days.
• Parents should be educated about the signs and symptoms to look for.
• The newborn bloodspot screening test should be carried out as usual on day 5-7.

• If any concerns are not able to be clarified with the neonatologists, the adult endocrinologist (Dr E Ward 07740 932931) may be contacted about maternal thyroid status or the paediatric endocrinologist for any newborn infants blood tests (0113 3923700)

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