Thyroid disease in pregnancy

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Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. [1] Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. [2] Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. [1] The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. [1] The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. [3] If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. [1] Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards.This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid. [4]

Contents

The thyroid in pregnancy

Fetal thyroxine is wholly obtained from maternal sources in early pregnancy since the fetal thyroid gland only becomes functional in the second trimester of gestation. As thyroxine is essential for fetal neurodevelopment it is critical that maternal delivery of thyroxine to the fetus is ensured early in gestation. [5] In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency. [6] Thus, pregnant women require additional iodine intake. A daily iodine intake of 250 µg is recommended in pregnancy but this is not always achieved even in iodine sufficient parts of the world. [7]

Thyroid hormone concentrations in blood are increased in pregnancy, partly due to the high levels of estrogen and due to the weak thyroid stimulating effects of human chorionic gonadotropin (hCG) that acts like TSH. Thyroxine (T4) levels rise from about 6–12 weeks, and peak by mid-gestation; reverse changes are seen with TSH. Gestation specific reference ranges for thyroid function tests are not widely in use although many centres are now preparing them.[ citation needed ]

Hypothyroidism

Clinical evaluation

Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism respectively. [8] Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world. [9] [10] The presentation of hypothyroidism in pregnancy is not always classical and may sometimes be difficult to distinguish from the symptoms of normal pregnancy. A high index of suspicion is therefore required especially in women at risk of thyroid disease e.g. women with a personal or family history of thyroid disease, goitre, or co-existing primary autoimmune disorder like type 1 diabetes.[ citation needed ]

Risks of hypothyroidism on fetal and maternal well-being

Hypothyroidism is diagnosed by noting a high TSH associated with a subnormal T4 concentration. Subclinical hypothyroidism (SCH) is present when the TSH is high but the T4 level is in the normal range but usually low normal. SCH is the commonest form of hypothyroidism in pregnancy and is usually due to progressive thyroid destruction due to autoimmune thyroid disease.[ citation needed ]

Several studies, mostly retrospective, have shown an association between overt hypothyroidism and adverse fetal and obstetric outcomes (e.g. Glinoer 1991). [11] Maternal complications such as miscarriages, anaemia in pregnancy, pre-eclampsia, abruptio placenta and postpartum haemorrhage can occur in pregnant women with overt hypothyroidism. [12] [13] Also, the offspring of these mothers can have complications such as premature birth, low birth weight and increased neonatal respiratory distress. [14] Similar complications have been reported in mothers with subclinical hypothyroidism. A three-fold risk of placental abruption and a two-fold risk of pre-term delivery were reported in mothers with subclinical hypothyroidism. [15] Another study showed a higher prevalence of subclinical hypothyroidism in women with pre-term delivery (before 32 weeks) compared to matched controls delivering at term. [16] An association with adverse obstetrics outcome has also been demonstrated in pregnant women with thyroid autoimmunity independent of thyroid function. Treatment of hypothyroidism reduces the risks of these adverse obstetric and fetal outcomes; a retrospective study of 150 pregnancies showed that treatment of hypothyroidism led to reduced rates of abortion and premature delivery. Also, a prospective intervention trial study showed that treatment of euthyroid antibody positive pregnant women led to fewer rates of miscarriage than non treated controls. [17]

It has long been known that cretinism (i.e. gross reduction in IQ) occurs in areas of severe iodine deficiency due to the fact that the mother is unable to make T4 for transport to the fetus particularly in the first trimester. This neurointellectual impairment (on a more modest scale) has now been shown in an iodine sufficient area (USA) where a study showed that the IQ scores of 7- to 9-year-old children, born to mothers with undiagnosed and untreated hypothyroidism in pregnancy, were seven points lower than those of children of matched control women with normal thyroid function in pregnancy. [18] Another study showed that persistent hypothyroxinaemia at 12 weeks gestation was associated with an 8-10 point deficit in mental and motor function scores in infant offspring compared to children of mothers with normal thyroid function. [19] Even maternal thyroid peroxidase antibodies were shown to be associated with impaired intellectual development in the offspring of mothers with normal thyroid function. [20] It has been shown that it is only the maternal FT4 levels that are associated with child IQ and brain morphological outcomes, as opposed to maternal TSH levels. [5]

Management of hypothyroidism in pregnancy

Medications to treat hypothyroidism have been found to be safe during pregnancy. [21] Levothyroxine is the treatment of choice for hypothyroidism in pregnancy. Thyroid function should be normalised prior to conception in women with pre-existing thyroid disease. Once pregnancy is confirmed the thyroxine dose should be increased by about 30-50% and subsequent titrations should be guided by thyroid function tests (FT4 and TSH) that should be monitored 4-6 weekly until euthyroidism is achieved. It is recommended that TSH levels are maintained below 2.5 mU/l in the first trimester of pregnancy and below 3 mU/l in later pregnancy. [22] The recommended maintenance dose of thyroxine in pregnancy is about 2.0-2.4 µg/kg daily. Thyroxine requirements may increase in late gestation and return to pre-pregnancy levels in the majority of women on delivery. Pregnant patients with subclinical hypothyroidism (normal FT4 and elevated TSH) should be treated as well, since supplementation with levothyroxine in such cases results in significantly higher delivery rate, with a pooled relative chance of 2.76. [23]

Hyperthyroidism

Clinical evaluation

Hyperthyroidism occurs in about 0.2-0.4% of all pregnancies. Most cases are due to Graves’ disease although less common causes (e.g. toxic nodules and thyroiditis) may be seen. [24] Clinical assessment alone may occasionally be inadequate in differentiating hyperthyroidism from the hyperdynamic state of pregnancy. Distinctive clinical features of Graves’ disease include the presence of ophthalmopathy, diffuse goitre and pretibial myxoedema. Also, hyperthyroidism must be distinguished from gestational transient thyrotoxicosis, a self-limiting hyperthyroid state due to the thyroid stimulatory effects of beta-hCG . This distinction is important since the latter condition is typically mild and will not usually require specific antithyroid treatment. Red cell zinc may also be useful in differentiating the two. [25] Hyperthyroidism due to Graves’ disease may worsen in the first trimester of pregnancy, remit in later pregnancy, and subsequently relapse in the postpartum.[ citation needed ]

Risks of hyperthyroidism on fetal and maternal well-being

Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of severe pre-eclampsia and up to a four-fold increased risk of low birth weight deliveries. Some of these unfavourable outcomes are more marked in women who are diagnosed for the first time in pregnancy. A recent study has also shown that already high normal maternal FT4 levels are associated with a decrease in child IQ and gray matter and cortex volumes, similar to the effects of hypothyroidism. [5]

Uncontrolled and inadequately treated maternal hyperthyroidism may also result in fetal and neonatal hyperthyroidism [26] due to the transplacental transfer of stimulatory TSH receptor antibodies (TRAbs). [27] Clinical neonatal hyperthyroidism occurs in about 1% of infants born to mothers with Graves’ disease. Rarely neonatal hypothyroidism may also be observed in the infants of mothers with Graves’ hyperthyroidism. This may result from transplacental transfer of circulating maternal anti-thyroid drugs, pituitary-thyroid axis suppression from transfer of maternal thyroxine.[ citation needed ]

Management of hyperthyroidism in pregnancy

Ideally a woman who is known to have hyperthyroidism should seek pre-pregnancy advice, although as yet there is no evidence for its benefit. Appropriate education should allay fears that are commonly present in these women. She should be referred for specialist care for frequent checking of her thyroid status, thyroid antibody evaluation and close monitoring of her medication needs. Medical therapy with anti-thyroid medications is the treatment of choice for hyperthyroidism in pregnancy. [28] [29] Methimazole and propylthiouracil (PTU) are effective in preventing pregnancy complications by hyperthyroidism. [30] Surgery is considered for patients who suffer severe adverse reactions to anti-thyroid drugs and this is best performed in the second trimester of pregnancy. Radioactive iodine is absolutely contraindicated in pregnancy and the puerperium. If a woman is already receiving carbimazole, a change to propylthiouracil (PTU) is recommended but this should be changed back to carbimazole after the first trimester. This is because carbimazole can rarely be associated with skin and also mid line defects in the fetus but PTU long term also can cause liver side effects in the adult. Carbimazole and PTU are both secreted in breast milk but evidence suggests that antithyroid drugs are safe during lactation. [31] There are no adverse effects on IQ or psychomotor development in children whose mothers have received antithyroid drugs in pregnancy.Current guidelines suggest that a pregnant patient should be on PTU during the first trimester of pregnancy due to lower tetragenic effect and then be switched to methimazole during the second and third trimester due to lower liver dysfunction side effects.[ citation needed ]

Postpartum thyroiditis

Postpartum thyroid dysfunction (PPTD) is a syndrome of thyroid dysfunction occurring within the first 12 months of delivery as a consequence of the postpartum immunological rebound that follows the immune tolerant state of pregnancy. PPTD is a destructive thyroiditis with similar pathogenetic features to Hashimoto's thyroiditis. [32]

The disease is very common with a prevalence of 5-9% of unselected postpartum women. Typically there is a transient hyperthyroid phase that is followed by a phase of hypothyroidism. Permanent hypothyroidism occurs in as much as 30% of cases after 3 years, and in 50% at 7–10 years. The hyperthyroid phase will not usually require treatment but, rarely, propanolol may be used for symptom control in severe cases. The hypothyroid phase should be treated with thyroxine if patients are symptomatic, planning to get pregnant, or if TSH levels are above 10 mU/L. Long-term follow up is necessary due to the risk of permanent hypothyroidism.[ citation needed ]

Nearly all the women with PPTD have positive TPO antibodies. This marker can be a useful screening test in early pregnancy as 50% of women with antibodies will develop thyroid dysfunction postpartum. In addition some but not all studies have shown an association between PPTD and depression so that thyroid function should be checked postpartum in women with mood changes.[ citation needed ]

Related Research Articles

Hyperthyroidism Thyroid gland disease that involves an overproduction of thyroid hormone.

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

Thyroid Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

Hypothyroidism Endocrine disease

Hypothyroidism, also called underactive thyroid or low thyroid, is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

Congenital hypothyroidism hypothyroidism that is present at birth

Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem. Significant deficiency may cause excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, significant jaundice, and low body temperature.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

Myxedema Human disease

Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hyperthyroidism and (rare) paradoxical cases of hypothyroidism. In this latter sense, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. One manifestation of myxedema occurring in the lower limb is pretibial myxedema, a hallmark of Graves disease, an autoimmune form of hyperthyroidism. Myxedema can also occur in Hashimoto thyroiditis and other long-standing forms of hypothyroidism.

Hashimotos thyroiditis autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on there may be no symptoms. Over time the thyroid may enlarge, forming a painless goiter. Some people eventually develop hypothyroidism with accompanying weight gain, feeling tired, constipation, depression, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma.

Levothyroxine chemical compound

Levothyroxine, also known as L-thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency, including the severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken by mouth or given by injection into a vein. Maximum effect from a specific dose can take up to six weeks to occur.

Propylthiouracil chemical compound

Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is typically only used when methimazole, surgery, and radioactive iodine is not possible. It is taken by mouth.

Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as cretinism due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.

Thyroid disease type of endocrine disease

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

Carbimazole chemical compound

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodinating and coupling the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

De Quervains thyroiditis Thyroid disease

De Quervain's thyroiditis, also known as subacute granulomatous thyroiditis or giant cell thyroiditis, is a member of the group of thyroiditis conditions known as resolving thyroiditis. People of all ages and genders may be affected.

Goitrogens are substances that disrupt the production of thyroid hormones by interfering with iodine uptake in the thyroid gland. This triggers the pituitary to release thyroid-stimulating hormone (TSH), which then promotes the growth of thyroid tissue, eventually leading to goiter.

Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. It affects about 5-10% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring lifelong treatment.

Hypothalamic–pituitary–thyroid axis part of the neuroendocrine system responsible for the regulation of metabolism.

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

Thyroid hormones hormones produced by the thyroid gland

Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5′-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production.

Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/Iodide (Anti–Na+/I) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).

The sum activity of peripheral deiodinases is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.

References

  1. 1 2 3 4 Korevaar, Tim I. M.; Medici, Marco; Visser, Theo J.; Peeters, Robin P. (2017-08-04). "Thyroid disease in pregnancy: new insights in diagnosis and clinical management". Nature Reviews. Endocrinology. 13 (10): 610–622. doi:10.1038/nrendo.2017.93. ISSN   1759-5037. PMID   28776582. S2CID   24810888.
  2. Okosieme, OE; Marx, H; Lazarus, JH (Sep 2008). "Medical management of thyroid dysfunction in pregnancy and the postpartum". Expert Opinion on Pharmacotherapy. 9 (13): 2281–93. doi:10.1517/14656566.9.13.2281. PMID   18710353. S2CID   71280624.
  3. Korevaar, Tim I. M.; de Rijke, Yolanda B.; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W. V.; Steegers, Eric A. P.; Visser, Theo J.; Peeters, Robin P. (March 2017). "Stimulation of Thyroid Function by Human Chorionic Gonadotropin During Pregnancy: A Risk Factor for Thyroid Disease and a Mechanism for Known Risk Factors". Thyroid. 27 (3): 440–450. doi:10.1089/thy.2016.0527. ISSN   1557-9077. PMID   28049387.
  4. Spencer, Laura; Bubner, Tanya; Bain, Emily; Middleton, Philippa (2015-09-21). "Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health". The Cochrane Database of Systematic Reviews (9): CD011263. doi:10.1002/14651858.cd011263.pub2. PMID   26387772.
  5. 1 2 3 Korevaar, Tim I M; Muetzel, Ryan; Medici, Marco; Chaker, Layal; Jaddoe, Vincent W V; de Rijke, Yolanda B; Steegers, Eric A P; Visser, Theo J; White, Tonya; Tiemeier, Henning; Peeters, Robin P (September 2015). "Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study". The Lancet Diabetes & Endocrinology. 4 (1): 35–43. doi:10.1016/s2213-8587(15)00327-7. PMID   26497402.
  6. Smyth, PP; Hetherton, AM; Smith, DF; Radcliff, M; O'Herlihy, C (Sep 1997). "Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake". The Journal of Clinical Endocrinology and Metabolism. 82 (9): 2840–3. doi: 10.1210/jcem.82.9.4203 . PMID   9284707.
  7. WHO S, Andersson M, de Benoist B, Delange F, Zupan J (Dec 2007). "Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation". Public Health Nutrition. 10 (12A): 1606–11. doi: 10.1017/S1368980007361004 . PMID   18053287.
  8. Klein, RZ; Haddow, JE; Faix, JD; Brown, RS; Hermos, RJ; Pulkkinen, A; Mitchell, ML (Jul 1991). "Prevalence of thyroid deficiency in pregnant women". Clinical Endocrinology. 35 (1): 41–6. doi:10.1111/j.1365-2265.1991.tb03494.x. PMID   1889138.
  9. Mandel SJ. "Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects." Best Pract Res Clin Endocrinol Metab. 2004; 18: 213-24.
  10. Mandel, SJ (Jun 2004). "Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects". Best Practice & Research. Clinical Endocrinology & Metabolism. 18 (2): 213–24. doi:10.1016/j.beem.2004.03.006. PMID   15157837.
  11. Glinoer, D; Soto, MF; Bourdoux, P; Lejeune, B; Delange, F; Lemone, M; Kinthaert, J; Robijn, C; Grun, JP; de Nayer, P (Aug 1991). "Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions". The Journal of Clinical Endocrinology and Metabolism. 73 (2): 421–7. doi:10.1210/jcem-73-2-421. PMID   1906897.
  12. "Thyroid Disease & Pregnancy". Office on Women’s Health, U.S. Department of Health and Human Services. 1 February 2017. Archived from the original on 12 July 2017. Retrieved 9 December 2017.PD-icon.svgThis article incorporates text from this source, which is in the public domain.
  13. "Postpartum Thyroiditis" (PDF). American Thyroid Association. 2014. Retrieved 9 December 2017.
  14. Davis, LE; Leveno, KJ; Cunningham, FG (Jul 1988). "Hypothyroidism complicating pregnancy". Obstetrics and Gynecology. 72 (1): 108–12. PMID   3380497.
  15. Casey, BM; Dashe, JS; Wells, CE; McIntire, DD; Byrd, W; Leveno, KJ; Cunningham, FG (Feb 2005). "Subclinical hypothyroidism and pregnancy outcomes". Obstetrics and Gynecology. 105 (2): 239–45. doi:10.1097/01.AOG.0000152345.99421.22. PMID   15684146. S2CID   11231790.
  16. Stagnaro-Green, A; Chen, X; Bogden, JD; Davies, TF; Scholl, TO (Apr 2005). "The thyroid and pregnancy: a novel risk factor for very preterm delivery". Thyroid. 15 (4): 351–7. doi:10.1089/thy.2005.15.351. PMID   15876159.
  17. Negro, R; Formoso, G; Mangieri, T; Pezzarossa, A; Dazzi, D; Hassan, H (Jul 2006). "Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications". The Journal of Clinical Endocrinology and Metabolism. 91 (7): 2587–91. doi: 10.1210/jc.2005-1603 . PMID   16621910.
  18. Haddow, JE; Palomaki, GE; Allan, WC; Williams, JR; Knight, GJ; Gagnon, J; O'Heir, CE; Mitchell, ML; Hermos, RJ; Waisbren, SE; Faix, JD; Klein, RZ (Aug 19, 1999). "Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child". The New England Journal of Medicine. 341 (8): 549–55. doi:10.1056/NEJM199908193410801. PMID   10451459. S2CID   4654832.
  19. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ (Sep 2003). "Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study". Clinical Endocrinology. 59 (3): 282–8. doi:10.1046/j.1365-2265.2003.01822.x. PMID   12919150. S2CID   12993173.
  20. Pop VJ, de Vries E, van Baar AL, Waelkens JJ, de Rooy HA, Horsten M, Donkers MM, Komproe IH, van Son MM, Vader HL (Dec 1995). "Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?". The Journal of Clinical Endocrinology and Metabolism. 80 (12): 3561–6. doi:10.1210/jcem.80.12.8530599. PMID   8530599.
  21. "Hypothyroidism". National Institute of Diabetes and Digestive and Kidney Diseases. March 2013. Archived from the original on 5 March 2016. Retrieved 9 December 2017.
  22. Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A (Aug 2007). "Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 92 (8 Suppl): S1–47. doi: 10.1210/jc.2007-0141 . PMID   17948378.
  23. Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P (May–Jun 2013). "Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs". Human Reproduction Update. 19 (3): 251–8. doi: 10.1093/humupd/dms052 . PMID   23327883.
  24. Marx, H; Amin, P; Lazarus, JH (Mar 22, 2008). "Hyperthyroidism and pregnancy". BMJ (Clinical Research Ed.). 336 (7645): 663–7. doi:10.1136/bmj.39462.709005.AE. PMC   2270981 . PMID   18356235.
  25. Swaminathan, R. (2000-07-01). "Thyroid Function during Pregnancy". Clinical Chemistry. 46 (7): 1016–1017. doi: 10.1093/clinchem/46.7.1016 . ISSN   0009-9147. PMID   10894853.
  26. Zimmerman D (1999). "Fetal and neonatal hyperthyroidism". Thyroid. 9 (7): 727–33. doi:10.1089/thy.1999.9.727. PMID   10447021.
  27. Polak M, Le Gac I, Vuillard E, et al. (2004). "Fetal and neonatal thyroid function in relation to maternal Graves' disease". Best Pract Res Clin Endocrinol Metab. 18 (2): 289–302. doi:10.1016/s1521-690x(04)00019-3. PMID   15157841.
  28. Mestman JH (2004). "Hyperthyroidism in pregnancy". Best Pract Res Clin Endocrinol Metab. 18 (2): 267–88. doi:10.1016/j.beem.2004.03.005. PMID   15157840.
  29. Fumarola, A; Di Fiore, A; Dainelli, M; Grani, G; Carbotta, G; Calvanese, A (June 2011). "Therapy of hyperthyroidism in pregnancy and breastfeeding". Obstetrical & Gynecological Survey. 66 (6): 378–85. doi:10.1097/ogx.0b013e31822c6388. PMID   21851752. S2CID   28728514.
  30. Vissenberg, R.; Van Den Boogaard, E.; Van Wely, M.; Van Der Post, J. A.; Fliers, E.; Bisschop, P. H.; Goddijn, M. (2012). "Treatment of thyroid disorders before conception and in early pregnancy: A systematic review". Human Reproduction Update. 18 (4): 360–73. doi: 10.1093/humupd/dms007 . PMID   22431565.
  31. Mandel, SJ; Cooper, DS (Jun 2001). "The use of antithyroid drugs in pregnancy and lactation". The Journal of Clinical Endocrinology and Metabolism. 86 (6): 2354–9. doi: 10.1210/jcem.86.6.7573 . PMID   11397822.
  32. Muller, AF; Drexhage, HA; Berghout, A (Oct 2001). "Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care". Endocrine Reviews. 22 (5): 605–30. doi: 10.1210/er.22.5.605 . PMID   11588143.