Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

Jansen, Toyah A; Korevaar, Tim I M; Mulder, Tessa A M; White, Tonya; Muetzel, Ryan L.; Peeters, Robin P.; Tiemeier, Henning

doi:10.1016/s2213-8587(19)30153-6

Cited by 113 publications

(95 citation statements)

References 40 publications

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“…15 When looking at gestational age, the inverted U-shaped association was most evident at 8 weeks of gestation but after 14 weeks of gestation TSH was no longer associated with gray matter changes. 15 In this study, there was no association between maternal FT4 and offspring gray matter volume. 15 As well, no functional assessments were done on these children to correlate with the structural changes.…”

Section: Subclinical and Overt Hyperthyroidismmentioning

confidence: 95%

“…15 Maternal TSH showed an inverted U-shaped association with offspring total gray matter volume (P = .007) and with cortical gray matter volume (P = .022). 15 What does this study add? assessed between age 7 to 9 years old.…”

Section: Associations Of Hypothyroidism With Brain Structure and Nementioning

confidence: 98%

“…8,14 Therefore, in the first half of pregnancy the fetus relies heavily on maternal transfer of thyroid hormone. 15 Thyroid hormone receptors have been shown in fetal brain tissue. 16 Thyroid hormone passage (FT4 and FT3) from maternal to fetal circulation is regulated by deiodinase enzymes found on the placenta.…”

Section: Associations Of Hypothyroidism With Brain Structure and Nementioning

confidence: 99%

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Maternal thyroid disease and its effects on the fetus and perinatal outcomes

Huget-Penner

Feig

2020

Prenatal Diagnosis

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Thyroid disease is common in women of childbearing age and can have significant effects on the development of the fetus and perinatal outcomes. Maternal thyroid hormone is critical for proper fetal neurodevelopment, and the fetus relies on thyroid hormone from its mother for the first half of pregnancy. Both overt maternal hypothyroidism and overt maternal hyperthyroidism have been shown to be associated with adverse effects on central nervous system gray matter and neurocognitive development of offspring as well as increased obstetrical risks. Treatment of overt thyroid conditions improves outcomes. Subclinical maternal hypothyroidism may increase adverse neurocognitive and obstetrical outcomes although data are conflicting. To date, treatment of subclinical hypothyroidism has not shown benefit. Subclinical hyperthyroidism is well tolerated in pregnancy. Thyroid autoantibodies alone may also affect neurodevelopment and obstetrical outcomes; however, recent data have shown no improvement with levothyroxine treatment. Several rare maternal genetic thyroid conditions can affect the fetus including a thyroid‐stimulating hormone receptor mutation leading to hypersensitivity to human chorionic gonadotropin and thyroid hormone resistance. The thyroid plays a crucial role in fetal health and understanding it is important for optimal care.

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Section: Subclinical and Overt Hyperthyroidismmentioning

confidence: 95%

Section: Associations Of Hypothyroidism With Brain Structure and Nementioning

confidence: 98%

Section: Associations Of Hypothyroidism With Brain Structure and Nementioning

confidence: 99%

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Maternal thyroid disease and its effects on the fetus and perinatal outcomes

Huget-Penner

Feig

2020

Prenatal Diagnosis

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“…82 Since then, several studies have investigated more subtle associations between fetal thyroid hormone levels and brain function later in life. [83][84][85] In the adult, thyroid hormones also play an important role in the maintenance of brain function. 86 Thyroid hormones, both T4 and T3, are actively transported into the brain by several different transport proteins.…”

Section: Thyroid Hormones and The Brainmentioning

confidence: 99%

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism

Sjölin

Holmberg

Törring

et al. 2019

Thyroid

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Graves' disease (GD) is an autoimmune condition with elevated thyroid hormone levels and symptoms suggesting an affected brain. These symptoms often resolve with treatment but, for some patients, GD results in a long period of reduced wellbeing. The overall aim of this thesis is to characterize the consequences of GD with a special focus on the brain. Three studies were conducted with data from questionnaires and clinical assessments of patients with GD in both the hyperthyroid and the euthyroid phase. Paper I was a longitudinal cohort study that assessed long-term treatment results 6 10 years after the onset of GD. Among 1186 included patients, the 774 who were initially treated with antithyroid drugs had a 40% chance of being euthyroid without thyroid medication at follow-up. One in four patients did not feel fully recovered. Paper II was a longitudinal case-control study designed to characterize affective and cognitive symptoms in 65 premenopausal women with newly diagnosed untreated GD. At onset of GD, the patients were significantly more affected with depression, anxiety, and mental fatigue compared to controls. At follow-up after 15 months, these symptoms remained in a significant proportion of patients. Patients with eye symptoms or a history of psychiatric conditions were more likely to be affected with brain-related symptoms. Paper III was a longitudinal case-control study of 65 premenopausal women with newly diagnosed untreated GD designed to investigate the effect of GD on hippocampal volumes. At onset of GD, hippocampus and amygdala volumes of the patients were smaller compared to controls. These brain structures became larger with treatment and, after 15 months, only the left amygdala remained smaller than in controls. At inclusion, there was an inverse correlation between thyroid-stimulating hormone receptor antibody (TRAb) and the volumes of both amygdalae and the right hippocampus. There were also inverse correlations between TRAb and free triiodothyronine recovery and the recovery of most of the four assessed brain volumes. GD is a condition where a minority of patients can hope for a long-lasting restored thyroid function. A large proportion of GD patients do not feel recovered after 8 years. Mental fatigue is an important concept for understanding the brain-derived symptoms in GD. In summary, the studies demonstrate that Graves' hyperthyroidism has unexpected long-term consequences for many patients, provide extensive new data on the serious and chronic nature of GD, and show for the first time that GD is accompanied by reversible brain changes.

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“…Additionally, recent reports have indicated that clinically euthyroid pregnant women with TPO antibody have relative hypothyroidism (Loh et al 2016), and that there is a dose dependency of TPO antibody concentration in relation to thyroid function (Korevaar et al 2018). Recently, it has been shown that both low and high TSH levels in early pregnancy affect fetal brain volume (Jansen et al 2019). If thyroid function is mildly impaired by TPO antibody, clinically euthyroid pregnant women having TPO antibody might be managed without thyroid hormone treatment and subsequent disturbance in fetal and placental growth.…”

Section: Discussionmentioning

confidence: 99%

The Presence of Thyroid Peroxidase Antibody Is Associated with Lower Placental Weight in Maternal Thyroid Dysfunction

Ushijima

Furukawa

Sameshima

2019

Tohoku J. Exp. Med.

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Thyroid dysfunction (TD) is caused by thyroid peroxidase (TPO) antibody, as seen in Hashimoto's disease. TD is a common problem of reproductive age and may impair fetal development. Here, we determined the effect of TPO antibody on perinatal outcomes in Japanese women with TD before conception. A retrospective study involving cases of maternal TD with term singleton birth was conducted. The subjects with TD were divided into two groups according to the presence (n = 22) or absence (n = 20) of TPO antibody. The control groups matched for age, parity, and gestational weeks were selected for TPO antibody-positive (n = 44) and -negative TD subjects (n = 40), respectively. Using the standard curve of Japanese placental weight, the frequency of placental weight less than the 50th percentile (small placenta) was examined. Placental weight was lower among TPO antibody-positive TD subjects, compared with TPO antibody-negative TD subjects (p < 0.01). However, other outcomes were similar between the groups. Importantly, compared with control mothers, placental weight was significantly lower (p < 0.01), birth weight tended to be lower (p = 0.07), and the incidence of gestational diabetes mellitus was higher (p = 0.02) among TPO antibody-positive subjects. There was no significant difference in placental weight between TPO antibody-negative subjects and controls. The frequency of small placenta was significantly higher in TPO antibody-positive subjects (odds ratio: 16.7) even when considering diabetes and pregnancy induced hypertension. Thus, the presence of TPO antibody is associated with lower placental weight among Japanese women having TD.

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Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

Cited by 113 publications

References 40 publications

Maternal thyroid disease and its effects on the fetus and perinatal outcomes

Maternal thyroid disease and its effects on the fetus and perinatal outcomes

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism

The Presence of Thyroid Peroxidase Antibody Is Associated with Lower Placental Weight in Maternal Thyroid Dysfunction

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